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Andrographis

What is Andrographis

Andrographis also known as Andrographis paniculata, Chuān Xīn Lian, Nemone Chinensi, Chirayath, Kalmegh, green chiretta or “King of Bitters” (for its extremely bitter taste), is a plant that has been effectively used in traditional Chinese and Ayurvedic medicines for centuries for the treatment of upper and lower respiratory tract infection (cough, common cold and influenza), diarrhea, fever due to several infectious diseases, jaundice, as a health tonic for the liver and cardiovascular health, and as an antioxidant 1. In-vitro (test tube) and in-vivo (animal) studies indicate that Andrographis paniculata exhibits antibacterial 2, antioxidant 3, anti-inflammatory 4, anticancer 5, antimetastatic 6 and immunostimulating 7 properties. Andrographis paniculata is traditionally used as an antipyretic for relieving and reducing the severity and duration of symptoms of common colds and alleviating fever, cough and sore throats, or as a tonic to aid convalescence after uncomplicated respiratory tract infections 8, 9, 10. Either alone or in combination with other herbs, andrographis has been shown to reduce duration and severity of upper respiratory infections such as those associated with the common cold or flu. Kan Jang, a standardized extract of Andrographis paniculata and Eleutherococcus senticosus (Devil’s bush, Devil’s shrub or Siberian ginseng), has been studied in manufacturer-sponsored clinical trials for relief of respiratory symptoms from cold and flu 11, 12. An andrographis extract was found useful in treating symptoms of upper respiratory infection 13. A few meta-analyses suggest possible benefit with Andrographis paniculata to reduce cough frequency and severity 14, 15.

Andrographis is also used to improve sexual dysfunctions and serve as a contraceptive. Andrographis paniculata’s perceived “blood purifying” property results in its use in diseases where blood “abnormalities” are considered causes of disease, such as skin eruptions, boils, scabies, leprosy, gonorrhea, and chronic and seasonal undetermined fevers 16. Andrographis extract may benefit patients with ulcerative colitis 17. Andrographis may also reduced symptoms of rheumatoid arthritis 18. In as study involving sixty people with rheumatoid arthritis who were given either Andrographis paniculata tablets containing 30 mg of andrographolides or placebo tablets containing lactose three times a day for 14 weeks 18. There was some improvement in joint tenderness and function in the Andrographis group; however, there were no differences in the outcomes compared to placebo. Three of the participants in the Andrographis group reported headaches. Patients should use caution before using Andrographis paniculata herb as it may interact with many drugs.

Andrographis paniculata is an important medicinal plant of Andrographis genus. A total number of species of this genus varied in different reports, which comprises either 19 19, 28 20, 40 21, or 44 22 species. The exact numbers of species of Andrographis genus are not validated yet. Total number of chromosomes of Andrographis paniculata is 25 and 50 in gametophytic 23 and sporophytic 24 count, respectively. In addition, genotypic differences are important considerations to find out high yielding germplasms.

Andrographis paniculata is native to Taiwan, Mainland China, and India 1. It is also commonly found in the tropical and subtropical Asia, Southeast Asia, and some other countries including Cambodia, Caribbean islands, Indonesia, Laos, Malaysia, Myanmar, Sri Lanka, Thailand, and Vietnam 25. Andrographis paniculata plant is also found in different phytogeographical and edaphic zones of China, America, West Indies, and Christmas Island 25.

The aerial part of Andrographis paniculata is commonly in traditional medicine, contains a large number of chemical constituents, mainly lactones, diterpenoids, diterpene glycosides, flavonoids, and flavonoid glycosides; however, the whole plant or roots are mentioned for certain limited purposes in some manuscripts 16. Controlled clinical trials report Andrographis paniculata is safe and effective use for reducing symptoms of uncomplicated upper respiratory tract infections. Traditionally, the Andrographis paniculata plant was used as an infusion, decoction, or powder, either alone or in combination with other medicinal plants. In modern times, and in many controlled clinical trials, commercial Andrographis preparations have tended to be standardized extracts of the whole plant. Since many disease conditions commonly treated with Andrographis paniculata in traditional medical systems are considered self-limiting, its purported benefits need critical evaluation.

Table 1. The vernacular names of Andrographis paniculata

LanguageName
ArabicQuasabhuva
AssameseChiorta, Kalmegh
AzerbaijaniAcılar Şahı, Acılar Xanı (khanı)
BengaliKalmegh
BurmeseSe-ga-gyi
ChineseChuan Xin Lian
EnglishThe Creat, King of Bitters
FrenchChirette verte, Roi des amers
GujaratiKariyatu
HindiKirayat, Kalpanath,
IndonesianSambiroto, Sambiloto
JapaneseSenshinren
KannadaNelaberu
KonkaniVhadlem Kiratyem
LaoLa-Sa-Bee
MalayHempedu Bumi, Sambiloto
MalayalamNelavepu, Kiriyattu
ManipuriVubati
MarathiOli-kiryata, Kalpa
MizoHnakhapui
OriyaBhuinimba
PanjabiChooraita
PersianNain-e Havandi
PhilippinesAluy, Lekha and Sinta
RussianAndrografis
SanskritKalmegha, Bhunimba and Yavatikta
ScandinavianGreen Chiratta
SinhaleseHīn Kohomba or Heen Kohomba
SpanishAndrografis
TamilNilavembu
TeluguNilavembu
ThaiFa-Talai-Jorn, Fah-talai-jon (jone)
TurkishAcılar Kralı, Acı Paşa, Acı Bey
UrduKalmegh, Kariyat, Mahatita
VietnameseXuyên Tâm Liên
[Sources 26, 27 ]

Figure 1. Andrographis paniculata

Andrographis paniculata

Is Andrographis paniculata safe?

In studies on humans, Andrographis paniculata has only been associated with rare and minor side-effects; however, a small number of cases of urticaria (a skin reaction characterised by sudden wheals or papules, accompanied by severe itching) have been reported 28. The trial reported in this study used 30 mg andrographalides, three times a day. Taking large doses of Andrographis may cause gastric discomfort, vomiting and loss of appetite.

You should be cautious about taking Andrographis paniculata if you take any of the following drugs because Andrographis may interact with them:

  • paracetamol/acetaminophen
  • anticoagulants
  • anti-hypertensives
  • immunosuppressants
  • insulin/oral hypoglycaemic agents.

Andrographis paniculata bioactive compounds

The aerial parts of Andrographis paniculata have been described for its innumerous use in the extraction of phytoconstituents; however, the leaves, stems, roots, and whole plants have also been reported for phytochemicals with pharmacological activities 1. The compositions of phytochemicals widely differ in terms of the part used, geography, season, and time of harvesting. Andrographolide, a diterpene lactone compound, is believed to be the principal active agent found in various parts of Andrographis paniculata, but particularly in the leaves (see Figure 3) 29. The chemical name of andrographolide is 3α, 14, 15, 18-tetrahydroxy-5β, 9βH, 10α-labda-8, 12-dien-16-oic acid γ-lactone and its molecular formula and weight are C20H30O5 and 350.4 (C 68.54%, H 8.63%, and O 22.83%), respectively 30. The structure of andrographolide has been analyzed by using X-ray, 1H,13 C-NMR, and ESI-MS 31. Although andrographolide is not very soluble in water, it is soluble in acetone, chloroform, ether, and hot ethanol. Crystalline andrographolide was reported to be highly stable, over a period of three months 32. Rajani et al. 33 reported a simple and rapid method for isolating andrographolide from the leaf of Andrographis paniculata. They extracted it using a 1 : 1 mixture of dichloromethane and methanol and then isolated the andrographolide directly from the extract by performing recrystallization. The purity of the compound has been evaluated with thin-layer chromatography (TLC), UV absorption spectrum, high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LCMS), and differential scanning calorimetry (DSC), which revealed the melting point of andrographolide to be 235.3°C 34.

Other possibly active constituents include neoandrographolide, andrographiside, 14-deoxy-11,12-didehydroandrographolide, deoxyandrographolide, and arabinoglycan proteins. 5-Hydroxy-7,8-dimethoxy (2R)-flavanone-5-O-beta-D-glucopyranoside, 5-hydroxy-7,8,2′,5′-tetramethoxy-flavone-5-O-beta-D-glucopyranoside, andrographic acid, and andrographidine A have also been isolated from Andrographis paniculata 35.

M. Sharma and R. Sharma 26 reported that the highest amount of andrographolide, a major bioactive compound of Andrographis paniculata, was found in the sample harvested after 110 days of cultivation followed by that just before flowering stage (130 days). The bioactive compounds were extracted with different types of solvents such as methanol (MeOH), ethanol (EtOH), hexane, acetone, acetone-water, chloroform (CHCl3), and dichloromethane from the whole plant, leaves, aerial parts, stems, and roots. Extraction procedure of bioactive compounds of Andrographis paniculata from methanol extracts, for example, is shown in Figure 2. In this extraction procedure, whole plant material of Andrographis paniculata (11.5 kg) was shade dried, ground, extracted with methanol (10 L × 6) under reflux for 8 h, and filtered to give residue. After filtration, three residues of the extract were found: (i) CHCl3 residue (700 g), (ii) H2O soluble (1.5 kg), and (iii) H2O insoluble residue (150 g). The residues were then chromatographed to get specific fractions. These fractions were further chromatographed and followed several procedures to identify specific compound. A total of 32 bioactive compounds with seven ent-labdane diterpenoids, twelve flavonoids, and two quinic acid derivatives have been isolated and characterized by this procedure. Previous phytochemical studies of Andrographis paniculata have reported more than 55 ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 4 xanthones 36 and 5 noriridoids, namely, andrographidoids A, B, C, D, and E 37.

Zhang et al. 38 reported 3 new ent-labdane diterpenoids, namely, 19-norandrographolides A, B, and C from the ethanol extracts of the aerial parts of Andrographis paniculata. Their structures have been established by HRESIMS and NMR spectral data in combination with X-ray crystallographic analysis; thus the 19-norandrographolide-A was identified as 3-dehydro-14-deoxy-19-norandrographolide. However, there is no report for pharmacological activity of these three compounds. The quinic acids were extracted only from the whole plants using the methanol solvents and they are functioning as an antiplatelet aggregator 39. Recently, Arifullah et al. 40 demonstrated moderately potent antimicrobial and antioxidant activity of andrographolide and echiodinin extracted from acetone and methanol extracts of in vitro leaf callus of Andrographis paniculata. Their structure elucidation was determined by electrospray ionization, MSD, NMR, and IR spectra. The yield of this compound was higher compared to the field plant. On the other hand, a novel flavonoid, 7, 8-dimethoxy-2′-hydroxy-5-O-β-d-glucopyranosyloxyflavone, together with 15 known flavonoids was isolated from the aerial parts of Andrographis paniculata. The structure was elucidated on the basis of chemical and spectroscopic analysis. Significant antiproliferative activity of these flavonoids against human leukaemia HL-60 cell was also investigated 41. Dua et al. 42 investigated four xanthones (1,2-dihydroxy-6,8-dimethoxyxanthone; 1,8-dihydroxy-3,7-dimethoxyxanthone; 3,7,8-trimethoxy-1-hydroxyxanthone; 4,8-dihydroxy-2,7-dimethoxyxanthone) from roots of Andrographis paniculata using CHCl3 fraction and purity confirmed by HPLC. Xu et al. 43 isolated and established structure of 5 rare types of noriridoids with a known iridoid curvifloruside F from the ethanol extracts of roots. They also assayed antibacterial activity of these compounds, but none showed any inhibitory activity (MIC > 100 μg/mL).

Figure 2. Andrographis extract

Andrographis paniculata methanol extracts

Footnote: Andrographis paniculata methanol extracts. Yield of pure compounds is in bracket in mg. Their structures have been elucidated mainly by 1D and 2D NMR and MS spectroscopic methods.

Abbreviations: SGCC = silica gel column chromatography; TLC = thin layer chromatography, MeOH = methanol; EtOAc = ethyl acetate, CHCl3 = chloroform

[Source 39 ]

Figure 3. Andrographolide chemical structure

Andrographolide chemical structure
[Source 30 ]

Andrographis paniculata mechanism of action

The active constituents of andrographis are diterpenoid lactones known as andrographolides 44. They exhibit anti-inflammatory activity by inhibiting nitric oxide production and cyclooxygenase-2 expression 4. In mouse hepatocytes, andrographis induced mRNA expression of P450 subfamily members, CYP1A1 and CYP1A2, in a concentration-dependent manner 45. In other studies, andrographis extract demonstrated a calcium channel inhibition effect that can cause smooth muscle relaxation and decrease blood pressure and heart rate 46, as well as relaxation of the uterus 47. Andrographis extract also showed antiplatelet effects by inhibiting thrombin 48 and platelet activating factor 49. When given orally to mice, andrographis extract was shown to neutralize snake venom 50. In addition, andrographolides inhibit HIV-induced dysregulation of cell cycle and increased CD4+ lymphocyte levels in HIV-1 patients 51.

Andrographolides also demonstrate anticancer effects in preclinical studies. Activity against multiple myeloma cells may occur via TLR4/NF-kappaB signaling pathway inhibition 52. In human colorectal cancer cells, reversal of 5-FU resistance was attributed to elevated BAX expression 53. In addition, migration and invasion was inhibited through suppression of mRNA and matrix metalloproteinase (MMP)-7 protein levels 5, while MMP-2 activity was also identified 54. Inhibition of IL-6 expression and IL-6-mediated signals occurs in human prostate cancer cells 55. In non-small cell lung cancer cells andrographolides reduced invasiveness by suppressing the PI3K/Akt/AP-1 signaling pathway and inhibiting MMP-7 expression 6. Apoptosis in human hepatoma cells occurred via c-Jun N-terminal kinase induction 56 and caspase activation 57. Decreased adhesion of gastric cancer cells to endothelial tissue was attributed to inhibition of E-selection expression 58. Inhibition of tumor cell growth may also occur by stimulating cytotoxic T-lymphocyte production via IL-2 and IFN-gamma secretion 59. Andrographolides also enhanced doxorubicin-induced cell death in several human cancer cell lines, mainly through JAK-STAT suppression 60.

What is andrographis used for?

Andrographis paniculata is used as a traditional herbal medicine in Bangladesh, China, Hong Kong, India, Pakistan, Philippines, Malaysia, Indonesia, and Thailand 61 and in the Unani and Ayurvedic medicines, Andrographis paniculata is one of the mostly used medicinal plants 16. Ethnobotanically, the leaves and roots of Andrographis paniculata have been used since centuries in Asia and Europe to cure the wide spectrum of health ailments. However, the whole plant is also used for certain limited purposes.

Andrographis paniculata has been used in Traditional Medical Systems to:

  • relieve fever
  • relieve the symptoms of colds
  • alleviate sore throats
  • alleviate gastro-intestinal upsets and acute diarrhoea
  • aid recovery from mild respiratory tract infections.

Andrographis paniculata is traditionally used for the treatment of snake bite, bug bite, diabetes, dysentery, fever, and malaria 62. Due to its “cold property” activity, Andrographis is recommended to be used to get rid of the body heat in fevers and to dispel toxins from the body. The overall traditional uses of Andrographis paniculata in different traditional medicinal systems or countries are pointed out in Table 2. In addition, Andrographis paniculata is also widely used for medicinal purposes by the traditional practitioners, tribes, or community as a folklore remedies in different countries 63.

In recent times, commercial preparations of Andrographis paniculata plant extracts are also used in certain western countries. However, the Andrographis paniculata preparations are yet need to be standardized for their better efficacy. The aerial part of Andrographis paniculata is most commonly used; its extracts contain diterpenoids, diterpene glycosides, lactones, flavonoids, and flavonoid glycosides 1. Whole Andrographis paniculata leaves and roots are also used as a folklore remedy for different diseases in Asia and Europe 27. Andrographis paniculata has been reported to have a broad range of pharmacological effects including anticancer 64, antidiarrheal 65, anti-hepatitis 66, anti-HIV 67, antihyperglycemic 68, anti-inflammatory 69, antimicrobial, antimalarial 70, antioxidant 71, cardiovascular 72, cytotoxic 67, hepatoprotective 73, immunostimulatory 74 and sexual dysfunctions 75.

Table 2. The ethnobotanical uses of Andrographis paniculata

Country/Traditional Medicinal Systems Traditional usesReference
AyurvedicFever, liver diseases, torpid liver, vitiligo76
JapanFever, common cold27
MalaysiaDiabetes, hypertension27
ScandinavianFever, common cold27
Traditional Bangladeshi medicineAcute diarrhea, anorexia, bloating with burning sensations in the chest, blood purifier, common cold, constipation, cough, debility, diabetes, dysentery, edema, emesis, fever, headache, helminthiasis, indigestion, intestinal worms, leucorrhea, liver disorders, loss of appetite, low sperm count, lower urinary tract infections, lung infections, malaria, mucus, pharyngotonsillitis, sexual and skin disorders, splenomegaly, uncomplicated sinusitis, vertigo61
Traditional Chinese medicineInflammation, fever, burn, carbuncle, cervical erosion, chicken pox, common cold, cough with thick sputum, detoxicant, detumescent, diarrhea dispel toxins of the body, dysentery, eczema, epidemic encephalitis B, fever, hepatitis, herpes zoster, laryngitis, mumps, neonatal subcutaneous annular ulcer, neurodermatitis, pelvic inflammation, pharyngitis, pharyngolaryngitis, pneumonia, respiratory infections, snake bites, sores, suppurative otitis media, tonsillitis, vaginitis16
Traditional Indian medicineDiabetes, dysentery, enteritis, helminthiasis, herpes, peptic ulcer, skin infections (topical use), snake-bites (topical use)27
Traditional Thai medicineFever, common cold, noninfectious diarrhea27
Unani system of medicineAnthelmintic, anti-inflammatory, antipyretic, aperient, astringent, boils, carminative, chronic and seasonal fevers, convalescence after fevers, diuretic, dysentery, dyspepsia associated with gaseous distension, emmenagogue, emollient, gastric and liver tonic, general debility, gonorrhea, irregular bowel habits, leprosy, loss of appetite, relieve griping, scabies, skin eruptions16

Common cold

Andrographis paniculata is commonly used for the prevention and treatment of common cold in several communities. A double-blind, placebo-controlled study of 61 adult patients suffering from common cold used Kan Jang tablets (made from Andrographis paniculata dried extract) for 5 days 77. Within the treatment period, significant clinical improvement was observed on day 4 for 1200 mg extract daily. Both groups showed significant reductions in clinical symptoms like shivering, sore throat, tiredness, muscular ache, rhinitis, sinus pains, and headache 77. A placebo-controlled study was conducted in 1997 using Kan Jang tablets on 107 healthy students in a rural school as a dose of 2 tablets (200 mg) per day for 3 months to evaluate its efficacy to prevent common cold. The common cold was successfully prevented by Kan Jang tablets with 2.1-fold higher prevention rate compared to the placebo group 78. Similar successful result was also demonstrated in another study including common cold with sinusitis in another place 79.

Andrographis and COVID-19

COVID-19 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in 2019 and has infected over 191 million people worldwide as of July 21, 2021 80. Common initial COVID-19 signs and symptoms include cough, fever, fatigue, headache, muscle aches and pain, and diarrhea 81. Some individuals with COVID-19 become severely ill, usually starting about 1 week after symptom onset; severe COVID-19 often involves progressive respiratory failure and may also result in life-threatening pneumonia, multiorgan failure, and death 82. In addition, thousands of individuals—possibly 10% to 75%—who have had COVID-19 report symptoms of “long COVID” (including fatigue, muscle weakness, sleep difficulties, and cognitive dysfunction) for several months after the acute stage of illness has passed 83. Studies conducted before the emergence of COVID-19 suggest that andrographis supplementation might reduce the severity of respiratory tract infections 84, 14. Because of these findings, some scientists believe that andrographis could help treat the symptoms of COVID-19, but studies have not thoroughly assessed use of this herb for this purpose 85, 86, 87, 88.

A few in vitro (test tube) studies suggest that andrographolide isolated from andrographis might bind the main protease of SARS-CoV-2, thereby inhibiting its replication, transcription, and host cell recognition 89. In a small clinical trial in Thailand 90, 91, researchers examined the effects of 60 mg or 100 mg andrographis extract called Fah Talai Jone in Thailand, given 3 times per day in 12 people with mild to moderate COVID-19 symptoms. COVID-19 symptoms, especially cough, improved within a few days after patients started taking the low dose (60 mg) andrographis, and all patients recovered after 3 weeks 92. No information was provided on the effects of the 100 mg andrographis dose. On the basis of these findings, a larger placebo-controlled trial was conducted among 60 participants, and Thailand’s health ministry subsequently approved a pilot program to use Fah Talai Jone for individuals aged 18 to 60 with minor symptoms within 72 hours of a COVID-19 diagnosis 92. One clinical trialexternal link disclaimer in Tibilisi, Georgia is examining whether a product called Kan-Jang® that contains andrographis and Eleutherococcus senticosus (2 capsules, 3 times per day for a total daily dose of 90 to 120 mg of andrographolides) for 2 weeks reduces the severity of inflammatory symptoms (including headache, loss of smell, nasal congestion, cough, muscle pain, and fever) in about 140 adults hospitalized with mild COVID-19 93. ClinicalTrials.gov does not list any other studies on the use of andrographis for managing COVID-19 symptoms. Whether the potential immunostimulatory effect of andrographis might worsen the cytokine storm associated with COVID-19 is not known 85.

Anti-inflammatory effect

The anti-inflammatory activity of Andrographis paniculata and its bioactive compounds (such as andrographolide and neoandrographolide) has been reported individually by many investigators 1. Andrographis paniculata extracts and andrographolide showed several anti-inflammatory activities, such as inhibition of intercellular adhesion molecule-1 expression in monocytes activated by tumor necrosis factor-α 94, suppression of inducible nitric oxide synthetase (iNOS) in RAW264.7 95, cyclooxygenase-2 (COX-2) expression in neutrophils and microglial cells 96, reduction of ERK1/2 phosphorylation in murine T cells 97 and IFN-γ, and IL-2 production 98, and inhibition of TNF-α and GM-CSF induced by lipopolysaccharide (LPS) 99. In a study conducted by Hidalgo et al. 96, andrographolide was analyzed for the activation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) induced by platelet-activating factor (PAF) and N-formylmethionyl-leucyl-phenylalanine (fMLP) in HL-60 cells differentiated into neutrophils. NF-κB controls or contributes to the transcription of more than 200 genes that are involved in a variety of physiological and pathophysiological processes, particularly in immunity and inflammation. It is a critical regulator of cell differentiation, proliferation, and apoptosis and plays pivotal roles in the normal organ development and tumorigenesis 100. However, the NF-κB can be activated via the signal transduction pathways which are multiple and complex. It was a surprising achievement that andrographolide significantly inhibited the binding of NF-κB to DNA, which is the final step of NF-κB activation and it also decreased the expression of cyclooxygenase-2 (COX-2) by inhibiting the activation of NF-κB in endothelial cells stimulated by PAF 101 and in microglial cells induced by lipopolysaccharide (LPS) 102. In addition, the kidney inflammation can also be recovered using andrographolide due to its ability to inhibit the NF-κB activated by LPS in kidney 103.

Oral administration of andrographolide at a dose of 300 mg/kg daily had shown significant analgesic activity on acetic-induced writhing in mice and on the Randall-Selitto test in rats, but there was no effect on the hot plate test in mice 104. Oral administration of andrographolide at 30, 100, and 300 mg/kg also showed anti-inflammatory activity in different models in rats 105. Iruretagoyena et al. 98 suggested that treatment with andrographolide at a daily dose equal to 4 mg/kg significantly reduced an inflammatory demyelinating disease of the central nervous system, autoimmune encephalitis by inhibiting T cells in mice. The balancing of proinflammatory and anti-inflammatory cytokines is the result of anti-inflammatory performance of andrographolide and regulation of Th1, Th2, and Th17 transcription factors. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions 106.

Besides the Andrographis paniculata and andrographolide, andrographolide derivatives (e.g., CHP1002 and andrographolide sulfonate) also exhibited anti-inflammatory properties 107. CHP1002, a novel synthetic derivative of andrographolide, significantly inhibited LPS-induced iNOS, COX-2 expressions, iNOS derived nitric oxide (NO), and COX-2 derived prostaglandin E2 (PGE2) production through the stimulation of heme oxygenase-1 (HO-1) expression in RAW264.7 macrophages. CHP1002 also significantly faded LPS-stimulated TNF-α, IL-1β, and IL-6 production 106. Liu et al. 107 demonstrated that intraperitoneal administration of andrographolide sulfonate, a water soluble andrographolide (trade name: Xi-Yan-Ping injection), attenuated the severity of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) induced colitis in mice. A dose of 1.25–5 mg/kg of andrographolide sulfonate significantly recovered the loss of body weights and diarrhea in colitis mice, prevented inflammatory damages of colons and proinflammatory cytokines such as IFN-γ, IL-17A, and TNF-α, and suppressed the functions of Th1 and Th17 which is a feasible strategy to control inflammatory bowel disease. The demonstrated results suggested that andrographolide sulfonate could be a strong therapeutic compound for the treatment of gastrointestinal inflammatory disorders 1.

Anti-diabetic effect

Inhibitions of alpha-glycosidase and alpha-amylase activity and stimulation of insulin sensitivity are considered as effective strategies to lower the level of postprandial blood glucose. These enzymes involved in digestion and absorption of carbohydrates resulting in postprandial increase of blood glucose 108. Insulin resistance is mainly expressed by hyperinsulinemia and high blood glucose level and is associated with some metabolic hormonal abnormalities, such as dyslipidemia, abnormal uric acid metabolism, increased ovarian testosterone secretion, endothelial dysfunction, elevated procoagulant factors, and elevated inflammatory markers 109. Andrographis paniculata extracts and andrographolide effectively showed antihyperglycemic effect by (a) lowering blood glucose level through inhibition of α-glycosidase and α-amylase 110; (b) increasing insulin sensitivity and thus stimulating glucose uptake and oxidation by peripheral tissues 111; (c) controlling abnormal lipid metabolism; (d) scavenging free radicals from circulation which disrupt the plasma membrane integrity resulting in decreased number of efficient plasma membrane receptors or transporter proteins necessary to uptake glucose from the blood stream 112. Blood sugar lowering effect of Andrographis paniculata was observed in both insulin-lacking diabetic rats and normal rats in several studies 68, 113.

Andrographolide at a dose of 50 mg/kg effectively decreased blood glucose level, stimulated GLUT4 translocation 113, and improved diabetic rat’s islet and beta cell functions 114. Glucose induced hyperglycemia (orally administered) has been prevented by water extracts of Andrographis paniculata in nondiabetic rats without affecting epinephrine-induced hyperglycemia 115. Oral administration of ethanol extracts of Andrographis paniculata significantly lowered the fasting blood glucose of human 116. Another bioactive compound, namely 14-deoxy-11,12-didehydroandrographolide, also showed the antihyperglycemic activity 117.

Besides controlling blood glucose level, andrographolide also effectively prevented the onset of insulitis in a dose dependent manner and thus delayed the onset and suppressed the development of diabetes in 30-week-old NOD mice 118. Andrographolide also regulates the Th1/Th2/Th17 homeostasis through which it may prevent β-cell death and inhibit T-cell infiltration into pancreatic islets and thereby prevent development of type 1 diabetes 118. Recently, Augustine et al. 112 reported that Andrographis paniculata decreases the blood glucose by increasing glucose utilization and oxidation, restoration of insulin signaling molecules in liver, and decreasing the serum lipid levels in high fat and sucrose induced type 2 diabetic rats without showing hypoglycemic effect. A combination of n-hexane insoluble fraction of Andrographis paniculata with curcuminoids fraction of Curcuma xanthorrhiza rhizome also significantly showed the antihyperglycemic effect on high-fructose-fat-fed rats 119. The combination of n-hexane insoluble fraction of ethanolic extract of Andrographis paniculata-curcuminoids fraction of Curcuma xanthorrhiza rhizome could be a potential source to develop an antidiabetic agent. Therefore, the identification of more antihyperglycemic compounds of Andrographis paniculata and combination of Andrographis paniculata with other medicinal plants would be a focusing point of researchers for the better treatment option of the diabetic patients.

Liver protective effect

Andrographis paniculata is widely used traditionally as a liver protective agent and a stimulating agent for multiple enzymes of the liver. It is also used as an ingredient in the polyherbal preparations for the treatment of hepatic disorders in Ayurvedic and Unani medicine 120. Along with different extracts of Andrographis paniculata, andrographolide, neoandrographolide, 14-dexoyandrographolide, and 14-deoxy-11,12-didehydroandrographolide compounds are also reported to have hepatoprotective effect 121. In a comparative study, the leaf extract and andrographolide was tested against the carbon tetrachloride- (CCl4-) induced hepatic microsomal lipid peroxidation. Only the leaf extract completely protected the high concentration CCl4-induced microsomal lipid peroxidation in vitro but not the andrographolide, which indicated that the hepatoprotective role is not solely due to the presence of andrographolide 122. Similar effect of crude alcohol extracts of the Andrographis paniculata leaves against carbon tetrachloride- (CCl4-)-induced liver damage was also reported by Rana and Avadhoot 123. Handa and Sharma 124 reported that andrographolide, methanol extract of whole plant, and andrographolide-free methanol extract improved liver histology in rats by 48.6%, 32%, and 15%, respectively, after CCl4-induced liver injury. Verma et al. 125 reported the effect of ethanol extract of Andrographis paniculata on restoration of different enzyme after CCl4-induced liver injury. Further research using specific bioactive compounds is demanding for the better understanding of the hepatoprotective role played by the Andrographis paniculata.

Antibacterial effect

Modern research has investigated the causes of extensive uses of Andrographis paniculata in traditional healing systems as an antimicrobial agent to treat a variety of health morbidities of infectious origin. Leelarasamee et al. 126 reported that crude powder suspended in water to be devoid of in vitro antibacterial activity against Salmonella, Shigella, Escherichia coli, gram A Streptococci, and Staphylococcus aureus, even at a concentration of 25 mg/mL crude powder. However, over the last 3 decades, researchers reported that different types of extracts of Andrographis paniculata possess potent antibacterial activity against various pathogenic and nonpathogenic bacteria. Nakanishi et al. 127 reported antibacterial activity of aqueous methanol (50% v/v) crude extracts of whole plant against Bacillus subtilis and Proteus vulgaris. Although Nakanishi et al. 127 reported the negative result against E. coli, ethanol extracts of aerial parts of Andrographis paniculata were found to be effective in inhibiting E. coli growth along with other ten gram positive and gram negative bacteria species in an investigation conducted by Mishra et al. 128. The aqueous extract showed significant antibacterial activity due to the combined effect of the isolated andrographolides and arabinogalactan proteins 129. Similar effect was also mentioned by Fabricant and Farnsworth 130.

The antibacterial activity of three different extracts (dichloromethane, methanol, and aqueous) of Andrographis paniculata whole plant was evaluated by Sule et al. 131 against 12 skin infection causing pathogenic bacterial strains. The extracts showed significant effects against all the tested bacterial strains in different concentrations likely 1000, 500, and 250 μg/disc. However, methanol extract showed the highest antibacterial activity against Enterococcus faecalis at 1000 μg/disc with an inhibition zone of 24 mm, and dichloromethane extract showed the least activity against Neisseria meningitis at 250 μg/disc with an inhibition zone of 6 mm. Similar results again were reported in another manuscript by Sule et al. 132 in the following year. In their study, they investigated antibacterial activity of methanol extract of whole plant against five human pathogenic bacteria S. aureus, Streptococcus pyogenes, Micrococcus luteus, Proteus mirabilis, and Pseudomonas aeruginosa. Their results revealed that the highest inhibition (19.67 ± 0.76 mm) was exerted against Staphylococcus aureus at 1000 μg/mL and the least (07.00 ± 1.50 mm) activity shown against Pseudomonas aeruginosa at 250 μg/mL. However, it was a noteworthy result that the methanol extract exhibited more potent inhibitory activity against Staphylococcus aureus (19.67 ± 0.76 mm) and Streptococcus pyogenes (16.00 ± 0.58 mm) at 1000 μg/mL compared to the antibiotic vancomycin (17.00 ± 1.05 mm and 14.50 ± 1.00 mm, resp.) 133. Furthermore, they isolated and characterized two important antibacterial bioactive compounds, namely, 14-deoxyandrographolide (Figure 2) and 3-O-β-D-glucosyl-14-deoxyandrographolide, from the whole plant of Andrographis paniculata and concluded that the mentioned efficacy of methanol extract had been shown due to the presence of these compounds.

Antiviral effect

Researchers investigated significant antiviral activity of Andrographis paniculata besides other pharmacological activities in last two decades. Although they reported antiviral activity against limited viruses, such as dengue virus serotype 1 (DENV-1) 134, human papilloma virus type 16 (HPV16) 135, herpes simplex virus type 1 (HSV-1) 136, influenza A virus 137 and HIV 138, their findings were very encouraging and noteworthy considering the life threatening role of these viruses in human community. The hot aqueous aerial parts extract of Andrographis paniculata was reported for its significant antiviral activity to reduce the percentage of HIV antigen-positive H9 cells 139. Recently, Tang et al. 134 reported that the methanol extract of Andrographis paniculata possesses significant inhibition activity against DENV-1 in vitro assay. Another study has revealed that andrographolide suppressed HPV16 transcription activity, leading to the reduction of E6 oncoprotein and restored p53 135.

Several bioactive compounds such as andrographolide, neoandrographolide, dehydroandrographolide, natural derivatives of andrographolide, namely, 14-deoxy-11,12-didehydroandrographolide and 14-deoxyandrographolide, and synthetic derivatives, namely, dehydroandrographolide succinic acid monoester (DAMS), 14-ά-lipoyl andrographolide (AL-1), 14-acetyl-3,9-isopropyl-ideneandrographolide, 14-acetylandrographolide, 3,14,19-triacetylandrographolide, and 3,9-isopropyl-ideneandrographolide have been shown to have significant antiviral activity against HIV, influenza A, and HSV-1 without any significant cytotoxic effect at virucidal concentrations. Andrographolide, isolated from ethanol extracts of whole plant of Andrographis paniculata, showed a great promise in the treatment of HIV infections. It might be able to inhibit viral replication by interfering CDK (cyclin dependent kinase) activity, resulting in deregulation of HIV induced cell cycle 140. The overall findings of andrographolide effects against different viruses indicate that andrographolide would be an effective agent for prevention and treatment of viral diseases.

Antiparasitic effect

Antiparasitic activity of the Andrographis paniculata extract is reported in certain articles. Dua et al. 42 investigated both in vitro and in vivo antimalarial activity of four xanthones isolated from roots against Plasmodium falciparum and Plasmodium berghei. One of the xanthones, 1,2-dihydroxy-6,8-dimethoxy-xanthone, showed substantial antiplasmodial activity during in vitro (4 μg/mL at IC50 value) and in vivo (62% parasitaemia reduction at 30 mg/Kg dose) study.

The water extract of dried leaves was found to be active against adult worms of Brugia malayi in vitro 141. Recently, Padma et al. 142 evaluated the aqueous and methanol extracts for in vitro anthelmintic activity against adult earth worms Pheretima posthuma. The extracts showed significant results at the concentrations of 25 mg/mL, 50 mg/mL, and 75 mg/mL. However, the clinical relevancies of the antiparasitic studies are inconclusive due to obtaining the results at high concentration that may not be feasible clinically.

Anticancer effect

Andrographolide exhibited both direct and indirect effects on cancer cells by inhibiting proliferation of cancer cells, cell-cycle arrests, or cell differentiation, enhancing body’s own immune system against cancer cells; and inducting apoptosis and necrosis of cancer cells 143. Dichloromethane fraction of methanol extract significantly inhibited the proliferation of HT-29 colon cancer cells. The major bioactive compound of Andrographis paniculata, andrographolide, isolated from dichloromethane inhibited the growth of a diverse cancer cell representing different types of human cancers 144. In contrast, recently Aditya et al. 145 reported that methanol extract of Andrographis paniculata was found to be very less effective against both MCF-7 breast and HT-29 colon cancer cell lines. This low activity exhibited might be due to the low penetration power of the active principles.

Antiproliferative activities of andrographolide and isoandrographolide along with other 16 ent-labdane diterpenoids isolated from 85% ethanol extract of Andrographis paniculata against human leukaemia HL-60 cells have also been investigated by Chen et al. 146. These results showed that andrographolide and isoandrographolide were more effective than others. In a recent study, Chen et al. 41 identified a new flavonoid, 7, 8-dimethoxy-2′-hydroxy-5-O-β-d-glucopyranosyloxyflavone, isolated from the aerial parts of Andrographis paniculata. This flavonoid exhibited potent antiproliferative activity against human leukaemia HL-60 cells with IC50 of 3.50 μM. Ethanol (70%) extracts and andrographolide were also found to be effective to increase the life spans of thymoma injected mice cells in an in vivo study 147. In the following year, Geethangili et al. 148 showed the effective cytotoxic activity of ethanol extracts against human cancer cells including Jurkat (lymphocytic), PC-3 (prostate), HepG2 (hepatoma), and colon 205 (colonic) cancer cells. In another study, use of andrographolide at a dose 12 μg/mL for 36 hours against HL-60 cells improved 27% in G0/G1 phase cells and significantly decreased cells number at S and G2/M phase 149. Shi et al. 150 reported that andrographolide can inhibit human colorectal carcinoma Lovo cell growth by G1–S phase arrest and induce the expression of cell-cycle inhibitory proteins p53, p21, and p16. These proteins repressed the activity of cyclin D1/Cdk4 and/or cyclin A/Cdk2, required for G1 to S phase transition. In a recent in vitro study, andrographolide has been shown to suppress the growth and invasion of colorectal carcinoma Lovo cells and trigger apoptosis. Besides the effect of andrographolide alone, andrographolide in combination with chemotherapeutics, cisplatin, is likely to represent a potential therapeutic strategy for colorectal carcinoma 151.

Andrographolide and its analogues exert direct inhibitory effect on cancer cells by inducing expression of cell cycle inhibitory proteins and depressing cyclin-dependent kinase (Cdk) resulting in blocking the cell cycle progression at G0/G1 152. Some other compounds also block the cell cycle progression at G2/M phase 148. A novel semisynthetic analogue of andrographolide, DRF3188, exhibited anticancer activities against MCF 7 breast cancer cells at a lower dosage than andrographolide through similar mechanism 153. Both the compounds block cell cycle at the G0-G1 phase through induction of the cell cycle inhibitor (p27) and concomitant decrease in the levels of Cdk4. Therefore, attention has been focused on the anticancer properties of pure components of Andrographis paniculata and the molecular target of andrographolide that blocks G1 stage still needs to be determined.

Immune system modulatory effect

Control of immune response by regulating nuclear factor of activated T cells (NFAT), a transcription factor essential for cytokine production during T-cell activation, is a widely known strategy. Preventing translocation of nuclear factor of activated T cells (NFAT) to nucleus is the target of several immunosuppressive agents (e.g., cyclosporin A, FK506) 154. Andrographis paniculata is known to exert several immunomodulatory properties. More than two decades ago, a laboratory test demonstrated that Andrographis paniculata inhibited growth of human breast cancer cells similar to the drug tamoxifen 155. Amroyan et al. 156 reported that andrographolide was effective to stop the clumping of blood platelets that lead to heart attacks and they also suggested that andrographolide has a major effect on activating the general defense functions of immune system by stimulating the production of antibodies as well as nonspecific immune responses such as increased macrophage phagocytosis. An in vitro study with the increased proliferation of lymphocytes and production of interleukin-2 (IL-2) confirmed the immunostimulatory activity of Andrographis paniculata 149. Three diterpene compounds of Andrographis paniculata isolated from dichloromethane fraction of methanol extract showed augmented proliferation and IL-2 induction in human peripheral blood lymphocytes (HPBLs) at a low concentration 144. In addition, the chronic consumption of the aqueous extract of Andrographis paniculata also promoted the immune functions at 250 mg/kg and 500 mg/kg; however, 1000 mg/kg dose leading to development of autoimmune reactions, anaemia and multiple myeloma 157. Andrographis paniculata extract and andrographolide significantly promoted the lyses of natural killer (NK) cell-mediated target cells on day 5 after tumor induction. Antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent complement-mediated cytotoxicity (ACC) in metastatic tumor bearing animals were also enhanced significantly compared to the control by the treatment of Andrographis paniculata extract and andrographolide. In addition, the levels of proinflammatory cytokines such as IL-1β, IL-6, GM-CSF, and TNF-α were also effectively reduced 158. Carretta et al. 154 demonstrated that andrographolide reduces IL-2 production, extracellular signal regulated kinase- (ERK-) 1 and ERK-5 phosphorylation induced by anti-CD3 or phorbol myristate acetate and ionomycin (PMA/Ionomycin), and NF-κB activity in Jurkat cells and this effect can be related to a reduction in NFAT activity and an increase in c-jun-N-terminal kinase (JNK) phosphorylation. Moreover, andrographolide inhibited tumor growth in animals by stimulating the production of cytotoxic T lymphocytes 147. Hence, the compounds modulate the host immune systems against these cells to confer the direct cytotoxicity to cancer cells. Based on the reported immunomodulatory properties, Andrographis paniculata and andrographolide might be effective clinically to treat the autoimmune diseases.

Cardiovascular effect

Cardiovascular diseases are the leading cause of death throughout the world. Andrographis paniculata is used widely for improving the cardiac health in traditional medicinal systems. Several studies have investigated its activities in cardiovascular diseases 1. Wang et al. 159 reported that Andrographis paniculata is potential to increase the nitric oxide, cyclic guanosine monophosphate, and superoxide dismutase activity with declines of lipid peroxide and endothelin in an atherosclerotic rabbit model. In another study, Wang and Zhao 160 also investigated that the Andrographis paniculata extracts can be able to prevent constriction of blood vessels and increase blood clotting time significantly in the pre- and postangioplasty procedures. The extracts inhibited the cell growth and DNA synthesis in a dose dependent manner, which is a similar mechanism like stents that prevent cell division.

Aqueous extracts and active constituents of Andrographis paniculata showed significant antihypertensive activity in both spontaneously hypertensive rats and normotensive Wister-Kyoto rats 161, improved the blood pressure status in both pre- and post experimental myocardial infarction in animals 162 and exhibited platelet antiaggregation in in vitro 156 and ex vivo 163 assays. The existing reports suggested that Andrographis paniculata can be used as alternative source of the treatment of cardiovascular diseases. Further studies are necessary to know the insight of the mechanism of actions of specific constituents of Andrographis paniculata and in clinical perspectives.

Antihyperlipidemic effect

Hyperlipidemia is an important factor for atherosclerosis that leads to heart attack (obstruction occurs in the coronary arteries) and stroke (obstruction occurs in the arteries of the brain) 164. Chen et al. 165 suggested the andrographolide as candidate therapeutic agent for atherosclerosis based on their research result. Recently, another study revealed antihyperlipidemic effects of andrographolide and neoandrographolide 166. Yang et al. 166 reported the effects of andrographolide and neoandrographolide on hyperlipidemic mice induced by 75% yolk emulsion and hyperlipidemic rats induced by high fat emulsion. Andrographolide and neoandrographolide reduced triglyceride, total cholesterol, and low-density lipoprotein cholesterol in a dose dependent manner. Plasma aspartate transaminase and alanine transaminase levels were also significantly reduced compared to the positive control (Simvastatin) 166. These compounds exhibited their lipid and lipoprotein reducing effects through downregulation of iNOS expression and upregulation of eNOS expression in aorta of hyperlipidemic rats 166. The results of hypolipidemic study require further exploration of the molecular mechanism and the related signaling pathway.

Sexual functions and contraceptive effect

Andrographis paniculata and andrographolide showed earlier either contraceptive 167, fertility 168 or no effects 169 in a variety of studies. Andrographis paniculata showed contraceptive effects by terminating spermatogenesis in male albino rats 170. Zoha et al. 171 reported that there were no pregnant female mice that consumed Andrographis paniculata mixed food daily after mating with the untreated male of potential fertility, which means that the Andrographis paniculata has contraceptive effect on female mice. Andrographis paniculata and andrographolide were effective to prevent cytokinesis of dividing spermatogenic cell lines resulting in stopped spermatogenesis 172. The antifertility effects of andrographolide are characterized by marked decreases of protein content along with significant increases of cholesterol, acid phosphatase, and alkaline phosphatase levels with appearance of fructose in the reproductive systems of rats 173. Panossian et al. 174 reported negative results of Andrographis paniculata’s powdered extract on blood progesterone content in rats. However, the testosterone level with mounting frequency was significantly increased in mice at 4 weeks of andrographolide treatment. There was no toxicity of andrographolide (50 mg/kg) treatment for up to 8 weeks on number and motility of sperm. Further studies are needed to confirm the double stand activities of Andrographis paniculata and andrographolide on female and male sexual behaviors. The investigation of specific mechanisms in regulation of fertility and contraceptive effects of Andrographis paniculata and its active constituents would be valued to identify target point of controlling sexual behaviors.

Andrographis paniculata benefits

Andrographis has been mostly studied for the treatment of colds, flu and upper respiratory infections. Lab studies suggest possible anticancer effects, but this has not been confirmed in humans. Several researches including in vitro (test tube), in vivo (animal) and clinical (human) studies have confirmed various pharmacological activities of Andrographis paniculata extracts and products. A primary modern use of Andrographis paniculata is for the prevention and treatment of the common cold. A wide range of pharmacological activities such as antiplatelet aggregation activity or antithrombotic actions 39, immunomodulatory activity 175 and other myriad health benefits 176 were observed among researches. Pharmacological and clinical studies suggest the potential for beneficial effects in diseases like cancer 177 and HIV infections 178. Andrographolide, a major ent-labdane diterpenoid of Andrographis paniculata, is the largest contributor of many pharmacological activities. Other ent-labdane diterpenoids (such as neoandrographolide and 14-deoxyandrographolide), flavonoids, quinic acids, and xanthones are also reported for their significant contributions.

Either alone or in combination with other herbs, andrographis has been shown to reduce duration and severity of upper respiratory infections such as those associated with the common cold or flu. Kan Jang, a standardized extract of Andrographis paniculata and Eleutherococcus senticosus (Devil’s bush, Devil’s shrub or Siberian ginseng), has been studied in manufacturer-sponsored clinical trials for relief of respiratory symptoms from cold and flu 11, 12. An andrographis extract was found useful in treating symptoms of upper respiratory infection 13. A few meta-analyses suggest possible benefit with Andrographis paniculata to reduce cough frequency and severity 14, 15.

There have now been at least eight randomized controlled trials published including more than 1000 subjects that have evaluated various andrographis derivatives in the treatment of acute respiratory infection, including pharyngitis 179. Systematic reviews by Coon and Ernst 180 and Poolsup et al. 181 conclude the following: “Collectively, the data suggest that Andrographis paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Andrographis paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted” 180. “Current evidence suggests that A. paniculata extract alone or in combination with A. senticosus extract may be more effective than placebo and may be an appropriate alternative treatment of uncomplicated acute upper respiratory tract infection” 181.

The most recent trial, not included in the reviews referred to previously, also reported positive results 182. Based on published evidence and with no evidence of serious safety concerns, it seems reasonable for adults to seek relief from acute respiratory infection symptoms with andrographis-based cold remedies 182. There is insufficient evidence to favor specific products, dosing regimen, or particular standardization procedures for phytochemical content. For pregnant women and children, it seems prudent to recommend against the use of andrographis because there is little data from studies in these populations to exclude risk of harm.

Andrographis has also been evaluated for ulcerative colitis. In one trial, those receiving Andrographis paniculata extract at higher doses were more likely to achieve a clinical response compared with placebo 17. Another study found it as effective as mesalamine in treating ulcerative colitis 183.

In other preliminary studies, andrographis extracts reduced rheumatoid factors and relieved rheumatoid arthritis symptoms 18. In patients with modest hypertriglyceridemia, a high-dose andrographis extract reduced triglyceride levels in a manner comparable to gemfibrozil 184.

Studies conducted in China have reported therapeutic value of andrographis extract in acute bacillary dysentery and gastroenteritis. Ethanol Andrographis extract tablets reportedly cured 88.3 percent of acute bacillary dysentery and 91.3 percent of acute gastroenteritis cases 185. Andrographolide administration was reported to cure 91 percent of acute bacillary dysentery cases 185. The same cure rate (91.1%) was achieved with a compound tablet containing andrographolide and neoandrographolide (at a ratio of 7:3) in cases of bacillary dysentery. This was reported to be higher than cure rates obtained with furazolidine or chloramphenicol 185.

In preclinical cancer studies, andrographolide exhibited activity against multiple myeloma stem cells 186, reversed 5-FU resistance in human colorectal cancer cells 53 and modulated P-glycoprotein-mediated multidrug resistance 187.

Andrographis paniculata dosage

The majority of studies for common colds and upper respiratory tract infection (URTI) used a patented product – Kan Jang – which combines Andrographis paniculata and Eleutherococcus senticosus (Devil’s bush, Devil’s shrub or Siberian ginseng). Andrographis used in this product is standardized to contain 4-6 percent andrographolides and the dose used provided anywhere from 60-72 mg per day (low range) up to about 300 mg per day (highest dose). Existing evidence suggests that best results might be obtained if taken within the first 24 hours of URTI symptoms.

Do Not take Andrographis paniculata if:

  • You are taking chemotherapy drugs: Andrographis has antioxidant effects and may interfere with the actions of chemotherapy drugs 188.
  • You are taking drugs that are substrates of cytochrome P450: Although clinical relevance is yet to be determined, andrographis may make some of these drugs less effective and may increase the risk of side effects of others 189.
  • You are taking blood pressure-lowering drugs: Andrographis may have additional hypotensive effects 46. A study in healthy humans showed transient reductions in blood pressure when taking the suggested dose for common cold and respiratory tract infections 190.
  • You are taking anticoagulants or antiplatelet drugs: Some lab studies suggest andrographis may interfere with these drugs 48.
  • You are taking drugs that are substrates of UDP-glucoronosyltransferase (UGT) 2B7: Lab studies suggest andrographolide derivatives may increase the side effects of drugs metabolized by this enzyme 191.

Toxicity and dosing

The Lethal dose 50 (LD50) of the alcohol Andrographis extract, obtained by cold maceration, is 1.8 g/kg. The LD50 of andrographolide (yield 0.78% w/w from whole plant) in male mice through intraperitoneal route is 11.46 g/kg 192. LD50 (Lethal dose 50) is the amount of an ingested substance that kills 50 percent of a test sample. It is expressed in mg/kg, or milligrams of substance per kilogram of body weight. In the study on HIV-positive patients a dose of 1,500-2,000 mg of andrographolides was given daily for six weeks. Side effects were common and the study was discontinued early despite some improvements in CD4+ counts 193. Until definitive information on Andrographis paniculata and its constituents on reproduction is available, it would be prudent for both men and women to avoid this herb during desired conception and for women during pregnancy.

The safety of Andrographis paniculata extract (Kalmcold) in genotoxic tests has been reported and also the LD50 value has been determined to be more than 5 g/kg rat body weight in an oral acute toxicity study 194. Testicular toxicity as assessed by reproductive organ weight, testicular histology, ultra structural analysis of leydig cells and testosterone levels was not found after 60 days treatment of Sprague Dawley rats with ethanol extract of the dried herbs of Andrographis paniculata at doses of 20, 200 and 1 000 mg/kg suggesting the relative safe toxicity profile 195.

Andrographis paniculata side effects

Due to Andrographis paniculata’s extreme bitterness, it may cause vomiting. Some reported Andrographis paniculata side effects include allergic reaction, skin rash, gastric instability, fatigue, headache, vertigo, loss of appetite, lymphadenopathy (enlarged lymph nodes), pain in the lymph nodes, vomiting, diarrhea, altered taste, metallic taste, and nausea are also observed in overdosing of Andrographis paniculata extracts 15, 196, 197. Andrographis paniculata may elevate liver enzymes 183. It is suggested to avoid Andrographis paniculata during pregnancy due to ovulation preventive effects of the plant 171.

Adverse reactions case reports:

  • Anaphylaxis and allergic reactions: Caused by several different Andrographis paniculata preparations. Methanol extraction may increase risk of allergenicity 198.
  • Anaphylactic reaction: In an HIV patient on-study during week 4 51 .
  • Lymphadenopathy (enlarged lymph nodes): With very high doses 196.
  • Acute kidney injury: Following intravenous administration of andrographolides. Symptoms included flank pain, decreased urine output, and nausea or vomiting 199.

Few studies showed the toxic effect of Andrographis paniculata on reproductive system by damaging the Sertoli cell in male gonads in albino rats. A dose of 25 and 50 mg/kg body weight for a period of 48 days demonstrated that antispermatogenic effect 75, 172, 167. However, contradictory result was also demonstrated by numerous studies 200, 168, 169, 201, 202. The safety of Andrographis paniculata extracts regarding the oral acute toxicity (>17 g/Kg, Lethal Dose 50 [LD50]) 200, testicular toxicity (>1 g/Kg, LD50) 169 and genotoxicity (5 g/Kg, LD50) 201 has been reported. LD50 (Lethal dose 50) is the amount of an ingested substance that kills 50 percent of a test sample. It is expressed in mg/kg, or milligrams of substance per kilogram of body weight.

On review of literature based on traditional use of Andrographis paniculata, no cautions or contraindications were identified that referred to the potential for this herb to cause allergic reactions 28. However, literature sources based on current use of Andrographis paniculata recommend to avoid this herb in cases of known allergy or hypersensitivity to products that contain Andrographis paniculata or its constituents 203 or to plants of the Acanthaceae family, with a warning against injecting crude extracts of the herb due to the potential for anaphylactic reactions 204.

If you use a medicine that contains Andrographis paniculata and suspect that you are experiencing any signs or symptoms of an allergic reaction, stop using the product and consult a health professional.

Signs and symptoms of severe allergic reactions can include one or more of the following:

  • hives or welts (a red, itchy, lumpy rash, like mosquito bites)
  • a tingling feeling in or around the mouth
  • stomach pain, vomiting and/or diarrhea
  • facial swelling
  • difficulty with breathing and/or noisy breathing
  • swelling of the tongue
  • swelling and/or tightness in throat
  • difficulty talking and/or hoarse voice
  • loss of consciousness and/or collapse.

If you have any questions or concerns about these medicines, talk to a health professional.

Drug interactions

  • Cytochrome P450 substrates: Laboratory studies indicate andrographis extract inhibits 1A2, 2C9, 3A4 189. Some andrographis compounds also induce CYP1A1 205. Although clinical relevance is yet to be determined, these properties can affect the intracellular concentration of drugs metabolized by these enzymes.
  • Anticoagulants, antiplatelets: Although laboratory studies indicate possible inhibition of platelet aggregation 48, one study in rats suggests that andrographis extract does not interact with warfarin when used concomitantly 206. Patients taking anticoagulant or antiplatelet medications should use caution and consult their treating physician if considering the use of andrographis products.
  • Chemotherapy drugs: Andrographolides have been shown to have antioxidant effects 188, which may interfere with the actions of some chemotherapy drugs.
  • Blood pressure-lowering drugs: Laboratory studies indicate that andrographis may have additive hypotensive effects 46. In healthy subjects, A. paniculata at the normal therapeutic dose for the common cold and respiratory tract infections modulated various clinical parameters, including transient reductions in blood pressure 190.
  • UDP-glucoronosyltransferase (UGT) 2B7: Laboratory studies indicate that andrographolide derivatives inhibit UGT2B7, and can increase the side effects of drugs metabolized by this enzyme 191.
  • Aminophylline: Andrographis inhibits CYP1A2, which is involved in metabolizing aminophylline, resulting in increased risk of side effects from this drug 207.
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