- What is triphala ?
- Fruits of Triphala
- Main Chemical Constituents of Triphala
- Triphala benefits
- Triphala in gastrointestinal health
- Triphala in diabetes and for weight loss
- Stress-reducing potential of Triphala
- Triphala and cardiovascular health
- Antimicrobial potential of Triphala
- The Potential of Triphala in Oral Care
- Radioprotective effects of Triphala
- Anti-tumor activity of Triphala
- Antioxidant activity of Triphala and eye health
- Anti-inflammatory effects of Triphala
- Antiaging effects of Triphala
- Triphala and the gut microbiome
What is triphala ?
Triphala 1) is a herbal formulation composed of 3 fruits: Indian gooseberry Amalaki (Emblica officinalis), Bibhitaki (Terminalia belerica), and Haritaki (Terminalia chebula) in a 1:1:1 ratio. Triphala is mentioned throughout the ancient literature of Ayurvedic medicine as a tridoshic rasayana because it promotes longevity and rejuvenation in patients of all constitutions and ages 2). Triphala is classified as a tridoshic rasayana, meaning that the “energetics are appropriate for Vata, Pitta, and Kapha or all types of patients” 3). Charak, the great Indian Ayurvedic physician, describes rasayanas as having the qualities of supporting strength and immunity 4). Triphala has being traditionally used in India as therapeutic aid to regulate the process of digestion, mild laxative and antimicrobial properties in various ailments like prevention of dental caries/plaque formation, gingival health and periodontal diseases 5), 6), 7).
According to traditional Ayurvedic medicine, Triphala formulation is shown to have various medicinal properties which promote health, longevity of life when used in a proper manner 8). It is also shown to have anti-inflammatory, antioxidant, and antimicrobial properties (because of the gallic acid content), and is a known to be hepatoprotective in nature 9), 10), 11). Triphala is reported to correct constipation thus helping to improve digestion 12). Triphala can be ingested over a long period of time without any side effects 13). The phenolic and nonphenolic composition of triphala are active against both pathogenic and nonpathogenic bacterial strains 14), 15); when used as mouth wash, it effectively reduced the number of mutant streptococci in saliva 16).
Various studies have been done to evaluate the antifungal property of triphala 17).
Fruits of Triphala
Emblica officinalis (Amalaki)
Main chemical ingredient: Vitamin C, carotene, nicotinic acid, riboflavin, and tannins 18).
Amalaki is known by the botanical name Emblica officinalis and also known in Sanskrit as Dhatri (The nurse), which is a reference to its incredible healing properties. Amalaki can be taken individually in powder form, a decoction or as a confection. Amalaki fruit is known to be one of the best rasayanas in Ayurveda, with anti-oxidant and anti-aging properties. It has its beneficial role in cancer, diabetes, liver treatment, heart trouble, ulcer, anemia, and various other diseases. Similarly, it has application as immunomodulatory, anti-pyretic, analgesic, cytoprotective, anti-tussive, and gastroprotective agent. Additionally, it is useful in memory enhancing, ophthalmic disorders, and lowering cholesterol level. It is also helpful in neutralizing snake venom and as an anti-microbial agent against Escherichia coli, K. ozaenae, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, S. paratyphi A, S. paratyphi B and Serratiamarcescens. The drug is not reported to have any side-effects even after prolonged use 19).
Figure 1. Embilica officinalis (Indian gooseberry)
Terminalia chebula (Hiritaki or Black myrobalan)
Main chemical ingredient: Tannins, anthraquinones, and polyphenolic compounds 20).
Terminalia chebula is a plant species belonging to the genus Terminalia, family Combretaceae. The fruit of the tree has been used as traditional medicine for household remedy against various human ailments, since antiquity. Terminalia chebula has been extensively used in Ayurveda, Unani, and Homoeopathic medicine and has become a cynosure of modern medicine. Terminalia chebula is rich in tannin. The chief constituents of tannin are chebulic acid, chebulagic acid, corilagin, and gallic acid.
Terminalia chebula exhibited anti-bacterial activity against a number of Gram-positive and Gram-negative human pathogenic bacterial species. It also exhibits anti-fungal and anti-viral properties. It has also shown anti-mutagenic/anti-carcinogenic activity, antioxidant activity, adaptogenic and anti-anaphylactic activities, immunomodulatory activity, cytoprotective and radioprotective activity. It is also effective in hypolipidemia/hypercholesterolemia, improving gastro-intestinal motility with anti-spasmodic activity, diabetes, retinopathy, and wound healing 21).
Figure 2. Haritaki (Terminalia chebula)
Terminalia belerica (Bibhitaki)
Main chemical ingredient: Gallic acid, tannic acid, and glycosides 22).
Terminalia bellerica Roxb. (Combretaceae), commonly known as “belleric myrobalan” and locally as “bahera,” is a large deciduous tree, found throughout central Asia and some other parts of the world. Its fruit is used in folk medicine to treat asthma, cancer, colic, diarrhea, dysuria, headache, hypertension, inflammations, and pain. The plant is reported to contain termilignan, thannilignan, anolignan B, gallic acid, ellagic acid, ί-sitosterol, arjungenin, belleric acid, bellericosidem, flavonoids, and tannins. T. belerica possesses antioxidant, anti-spasmodic, bronchodilatory, hypercholesterolemic, anti-bacterial, cardioprotective, hepatoprotective, hypoglycemic, and hypotensive properties 23).
Figure 3. Bibhitaki (Terminalia belerica)
Main Chemical Constituents of Triphala
Tannin is a general descriptive name for a group of polymeric phenolic substances capable of tanning leather or precipitating gelatin from solution, a property known as astringency. This group of compounds, especially green teas and red wines, has received a great deal of attention in recent years since they can cure or prevent a variety of ills. Many human physiological activities, such as stimulation of phagocytic cells, host-mediated tumor activity, and a wide range of anti-infective actions, have been assigned to tannins. One of their molecular actions is to complex with proteins through so-called non-specific forces such as hydrogen-bonding and hydrophobic effects, as well as by covalent bond formation. Thus, their mode of anti-microbial action may be related to their ability to inactivate microbial adhesins, enzymes, and cell envelope transport proteins 24).
Quinones are aromatic rings with two ketone substitutions. They are ubiquitous in nature and are characteristically highly reactive. The individual redox potential of the particular quinine-hydroquinone pair is very important in many biological systems. Vitamin K is a complex naphthoquinone with anti-hemorrhagic activity. In addition to providing a source of stable free radicals, quinones are known to complex irreversibly with nucleophilic amino acids in proteins, often leading to inactivation of the protein and loss of function. For that reason, the potential range of quinone anti-microbial effects is great. Probable targets in the microbial cell are surface-exposed adhesins, cell wall polypeptides, and membrane-bound enzymes. Quinones may also render substrates unavailable to the microorganism 25).
Flavones, flavonoids, and flavonols
Flavones are phenolic structures containing one carbonyl group (as opposed to the two carbonyls in quinones). The addition of a 3-hydroxyl group yields a flavonol. Flavonoids are also hydroxylated phenolic substances, but occur as a C6-C3 unit linked to an aromatic ring. Since they are known to be synthesized by plants in response to microbial infection, it should not be surprising that they have been found in vitro to be effective anti-microbial substances against a wide array of microorganisms. Their activity is probably due to their ability to complex with extracellular and soluble proteins and to complex with bacterial cell walls. More lipophilic flavonoids may also disrupt microbial membranes. These compounds have been shown to inhibit Vibrio cholera O1, Shigella, Streptococcus mutansin vitro. Inhibition of isolated bacterial glucosyltransferases in S. mutans, and reduction of fissure caries by about 40% has also been demonstrated 26).
Gallic acid is a common phyto-constituent present in all three herbs used in Triphala. It is reported to possess hepatoprotective and antioxidant activity. It also suppresses growth of cancer cells.
Fruit juice of Emblica officinalis (Indian gooseberry Amalaki) contains the highest vitamin C (478.56 mg/100 mL) content. The fruit when blended with other fruits boosted their nutritional quality in terms of vitamin C content. Vitamin C in EO accounts for approximately 45-70% of the antioxidant activity 27). Evidences have been reported for the relation between vitamin C and periodontal disease. Significant gum bleeding can occur in vitamin C deficiency. Vitamin C along with bioflavonoid helps to speed up the healing process 28).
Ayurvedic physicians use Triphala for many ailments but most importantly to treat various gastrointestinal disorders, as digestive, mild laxative at normal doses, bowel tonic at low dose, purgative at high doses, carminative, expectorant, antispasmodic, and bronchodilator 29). Triphala is widely used to treat constipation, as an intestinal cleanser, as a gastrointestinal tract tonifier, to fasten peristalsis and to support both digestion and absorption of food. Triphala is also useful in maintaining serum cholesterol levels, to improve circulation, relax the bile duct and as a hepatoprotective agent 30). Daily use of Triphala may also promote proper digestion and absorption of food, reduce serum cholesterol levels, improve circulation, relax bile ducts, prevent immunosenescence, maintain homeostasis of the endocrine system, and increase production of red blood cells and hemoglobin 31).
The major active constituents of triphala are the tannins, gallic acid, ellagic acid, and chebulinic acid, which are potent antioxidants that may account, at least in part, for the observed immunomodulatory activity of the formula 32), 33), 34). Triphala also contains other bioactive compounds such as flavonoids (e.g., quercetin and luteolin), saponins, anthraquinones, amino acids, fatty acids, and various carbohydrates 35). In addition, Triphala-derived polyphenols such as chebulinic acid are also transformed by the human gut microbiota into bioactive metabolites, which have demonstrated potential in vitro to prevent oxidative damage 36).
Variable efficacy of herbal therapies
A number of factors, including variability in herbal source, processing, bioavailability, digestion, and absorption of herbal components, cause the true efficacy of herbs on human health to be highly variable. This variability is known to be at least partially due to inherent variation in the gut microbiota that act on the ingested components of herbal remedies and transform them into compounds with increased bioabsorption and bioactivity. These features have confounded the true efficacy of herbal remedies as it pertains to the maintenance of human health and/or the ability to reverse chronic disease states.
The increased popularity of herbal remedies such as Triphala has led to dramatic improvements in the processing of crude plant materials that serve to maximize the absorption of otherwise poorly absorbed plant components. Despite these improvements, these preparations still display pronounced variability in efficacy, which is likely related to the natural variation in composition of gut microbiota species that catalyze the biotransformation of herbal components. This response variability is not unique to herbs and, in fact, may be the case for virtually all health-promoting compounds ingested by humans (e.g., polyphenolic compounds derived from plants).
Triphala in gastrointestinal health
Triphala is perhaps most well known for its use in general gastrointestinal health. Animal studies have shown that both aqueous and alcohol-based extracts of Triphala prevent diarrhea 37). Triphala also induces enteroprotective effects, which are likely due, at least in part, to the high antioxidant content. In a rodent model, Triphala replenished depleted protein in the intestinal villi of the brush border as well as glutathione and phospholipid levels; the formula simultaneously decreased myeloperoxidase and xanthine oxidase levels in intestinal epithelium 38). In rats, Triphala exerted a gastroprotective effect on stress-induced ulcer 39). One human clinical trial that investigated the use of Triphala in patients with gastrointestinal disorders reported that treatment reduced constipation, mucous, abdominal pain, hyperacidity, and flatulence while improving the frequency, yield, and consistency of stool 40). Triphala also reduced colitis in a mouse model, and the treatment effect was attributed to antioxidant effects and high levels of flavonoids contained in Triphala 41).
Triphala in diabetes and for weight loss
Deregulation of eating behavior is common in industrialized countries. Studies have demonstrated the potential of Triphala as a therapeutic agent for weight loss and reduction of body fat. In an animal study, Triphala was administered for 10 weeks to diet-induced obese mice 42). Triphala treatment decreased the percentage of body fat, body weight, and energy intake. Triphala also decreased total cholesterol, triglycerides, and low-density lipoprotein cholesterol in the experimental group compared with the control group. In a 12-week, double-blind, randomized placebo-controlled trial, human subjects treated with Triphala lost ∼5 kg compared with the placebo control group 43). Mean fasting blood sugar and fasting serum insulin levels were also reduced in the treated compared with control subjects. Given the global obesity epidemic, more treatment options are necessary to reduce the associated healthcare burden.
Triphala exerts hypoglycemic effects. Patients with type 2 diabetes are likely to have high postprandial blood glucose levels, especially after consuming carbohydrates. Elevated blood glucose results from the breakdown of carbohydrates by the digestive enzymes, alpha-amylase and alpha-glucosidase, and the reduced ability of cells to take in glucose from the blood. Past studies report that Triphala may exert actions similar to diabetic pharmaceutical drugs by inhibiting digestive enzymes and may decrease absorption of glucose through inhibition of glycolytic enzymes, thereby reducing blood glucose levels. One study demonstrated the inhibitory potential of Triphala on pancreatic glycolytic enzymes, namely alpha-amylase and alpha-glucosidase, which break down larger polysaccharides into glucose molecules that enter the blood stream 44).
The role that Triphala plays in inhibiting starch digestion and absorption, thereby decreasing postprandial hyperglycemia, is similar to that of diabetes pharmaceutical drugs, such as miglitol and acarbose, which also target these glycolytic enzymes. In addition, Triphala decreased serum glucose levels in normal and alloxan-induced diabetic rats 45). A clinical study of noninsulin-dependent diabetes mellitus patients revealed that supplementation with 5 g of Triphala powder for 45 days significantly lowered blood glucose levels 46). Both fasting and postprandial blood glucose were reduced, which may be due to active ingredients such as sorbitol. Constituents in Triphala, including ellagitannins and gallotannins, also enhance both PPAR-alpha and -gamma signaling, which increase insulin responsiveness and glucose uptake without inducing adipogenesis 47). These polyphenols may also promote decreased blood glucose and insulin levels in diabetic patients.
Triphala may also protect diabetics and those predisposed to diabetes through inhibition of glycation enzymes. Elevated blood glucose can cause severe damage through the process of glycation, in which sugar molecules compromise protein molecules in the body, which may in turn lead to nerve damage or blindness. Due to the presence of tannins, Triphala extract was found to effectively inhibit protein glycation in vitro 48). Triphala may also prevent glycation through promotion of lower blood glucose levels. As diabetes is the most prevalent endocrine disease globally, increased access to complementary hypoglycemic therapies for integrative care is needed.
Stress-reducing potential of Triphala
Stress-induced disorders such as anxiety represent the leading causes of adult disability worldwide 49). Stress is a state of disharmony caused by perceived threat that is counteracted by an adaptive response to reestablish homeostasis and is associated with many chronic diseases. Animal studies have shown that Triphala protected against cold-induced stress and reversed stress-induced behavioral alterations and biochemical changes such as increased lipid peroxidation and corticosterone levels 50). Triphala also prevented noise-induced stress 51). In rats, Triphala prevented the noise-induced metabolic changes by mediating the antioxidant and cell-mediated immune response, and it was hypothesized that the biological mechanism is related to its antioxidant properties 52), 53). Modern humans experience high levels of stress, thus adaptogenic treatments are needed more extensively in clinical practice.
Triphala and cardiovascular health
Cardiovascular disease is a leading cause of mortality and morbidity worldwide, and hypercholesteremia is an important risk factor. Animal studies have reported the hypercholesteremic effects of Triphala. In one study, Triphala reduced the total cholesterol, low-density lipoprotein, very low-density lipoprotein, and free fatty acid levels in rats fed an atherogenic diet for 48 days 54). Another study in rats fed an atherogenic diet revealed that Haritaki, one of the herbs in Triphala, induced hypolipidemic effects in the herb-treated group. A reduction in total cholesterol, triglycerides, and total protein and elevation of high-density lipoprotein cholesterol were found in the herb-treated group compared with control group 55). Triphala is a powerful herb to address imbalances in the gastrointestinal tract and cardiovascular system and should be more widely studied in the context of these common diseases.
Antimicrobial potential of Triphala
Over administration of antibiotics has led to widespread drug resistance, thus it is becoming imperative that clinical researchers discover alternative and adjunctive antimicrobial agents with high efficacy. Both Triphala water decoctions (12%) and ethanol extracts (14%) have demonstrated antibacterial activity in vitro against bacterial isolates derived from patients infected with human immunodeficiency virus 56); the ethanol extracts were reported to have greater in vitro antimicrobial action against these species compared with the aqueous extracts, which may indicate lower solubility of the aromatic antibiotic compounds.
In addition, other studies report that these extracts also exert broad-spectrum antimicrobial action against antibiotic-resistant bacteria isolated from human subjects. The aqueous extracts (1:6) have demonstrated greater efficacy compared with the ethanol extracts (1:6) on pathogenic bacteria such as Escherichia coli and Staphylococcus aureus 57). In vitro, ethanol extracts of Triphala (100 mg/mL) components exhibited specific antimicrobial activity against multidrug-resistant clinical bacterial isolates 58). Thus, Triphala was reported to exert antibacterial effects on both gram-positive and gram-negative species in vitro and demonstrated potential for further investigation as a complementary or adjunct antimicrobial therapy.
In addition to antimicrobial effects against oral bacteria, Triphala has also demonstrated the potential to eradicate enteric pathogens in vitro. One study tested the effects of Triphala aqueous extract (200 mg/mL) against enteric bacterial pathogens in vitro and found that Triphala possesses strong antibacterial effects against Staphylococcus epidermidis and S. aureus and moderate effects against Proteus vulgaris, Pseudomonas aeruginosa, and Salmonella typhi 59). In addition to antibacterial effects, Triphala is also known to exhibit antifungal properties. Triphala exerts antifungal action against Asperigillus species and has been reported to inhibit the fungus by up to 37.96% in vitro. In particular, the aqueous extracts (1:1) of fresh fruits were found to be more effective than dry fruits 60). Thus, the formula represents a promising antimicrobial candidate in need of further study.
The Potential of Triphala in Oral Care
Triphala has been used traditionally in Ayurvedic medicine as an antimicrobial agent 61). Numerous controlled clinical trials have shown that Triphala significantly reduces the abundance of oral bacteria, dental plaque, and gingivitis in human subjects 62), 63). For example, Triphala is effective against Enterococcus faecalis, one of the most difficult to eliminate oral pathogens that are commonly isolated in chronic periodontitis. One study revealed that Triphala (5 mg/mL) in 10% dimethyl sulfoxide (DMSO) was equally or more effective at eliminating E. faecalis in vitro compared with NaOCl, a common irrigant used during root canals 64). Triphala was more effective than 0.5% and 1% NaOCl solution, but equally effective as 2.5% and 5% solutions.
In addition, another group reported that Triphala in 10% DMSO was more effective than 5.25% NaOCl solution against E. faecalis biofilms on ex vivo tooth substrate and suggested the extract as an alternative in the context of clinical root canal irrigation 65). A study using human primary teeth ex vivo revealed that Triphala suspended in 10% DMSO (1:3) exhibited significant antibacterial activity compared with control as well as higher antibacterial activity compared with 3% NaOCl 66). In vitro studies using Triphala ethanol extract have reported similar antimicrobial effects against E. faecalis compared with 2.5% NaOCl 67). Thus, Triphala may represent a potential therapy to eliminate E. faecalis as more side-effects and larger risk are associated with NaOCl solution treatment.
Dental caries, or cavities of the teeth, is a common infection associated with humans. Examining the use of Triphala as an oral antimicrobial agent, one study reported that Triphala dissolved in 10% DMSO exhibited a significant antibacterial effect ex vivo on extracted human mandibular premolars against Streptococcus mutans, which is one of the most prevalent oral pathogens responsible for dental cavities 68).
Human clinical trials using Triphala water decoction as a mouthwash report that it exerts comparable efficacy compared with chlorhexidine gluconate germicidal mouthwash in the prevention of dental caries.45,46 For example, a study in human subjects revealed that Triphala (6%) mouthwash promoted a significant reduction in oral streptococcus colonies. Oral streptococcus levels were measured after using a 6% Triphala mouthwash or 0.2% chlorhexidine mouthwash twice per day for 48 h and for 7 days; Streptococcus levels were reduced by 17% and 44%, respectively, in the Triphala-treated group 69). The researchers concluded that Triphala was as effective as 0.2% chlorhexidine mouthwash given that the results of the Triphala treatment were similar to the chlorhexidine-treated group. Another double-blind human clinical trial also reported significant reductions in oral streptococcus levels at 5 and 60 min after rinsing with 15 mL aqueous Triphala extract (10%) mouthwash 70).
In addition, a double-blind, randomized human clinical trial reported that Triphala (10%) mouthwash is effective against dental plaque and gingivitis in teenagers 71). The study reported Triphala as equally effective in antiplaque and antigingivitis activity compared with chlorhexidine. Moreover, a clinical study in children on the effects of Triphala (0.6%) mouthwash on dental plaque, gingival inflammation, and microbial growth also compared its efficacy with a commercially available chlorhexidine mouthwash. The results indicated that both the germicidal chlorhexidine (0.1%) and Triphala mouthwash were equally effective in reducing plaque and increasing gingival health after 9 months; however, Triphala was more effective than chlorhexidine in reducing microbial cell counts 72). A double-blind, randomized clinical trial in young adults also compared the efficacy of Triphala (0.6%) and chlorhexidine (0.12%) mouthwash for 21 days and reported a similar reduction in both plaque and gingival scores for both the Triphala- and chlorhexidine-treated groups 73). Triphala mouthwash treatment has also shown promise to reverse precancerous oral lesions associated with tobacco use in young adults 74).
In periodontal diseases, matrix metalloproteinases (MMPs) degrade extracellular matrix proteins in a spectrum of processes that include tissue remodeling such as the connective tissue destruction observed in periodontitis. Ex vivo Triphala studies using extracted gingival tissue have demonstrated a greater reduction of MMP-9 activity in patient-derived white blood cells treated with Triphala compared with patient-derived cells treated with the standard antibiotic drug 75). In treated tissue extracts, Triphala (1.5 mg/mL) reduced MMP-9 activity by 77%, while doxycycline (300 μg/mL) reduced MMP-9 activity by 59%. Thus, MMP inhibitors are important adjunctive therapies in periodontitis treatment and Triphala may represent a candidate to investigate in greater detail in this context. In addition, given the observed effectiveness of Triphala mouthwash compared with standard treatment, additional clinical trials should be performed to identify the potential for integration in dentistry.
Radioprotective effects of Triphala
Studies have concluded that Triphala may help prevent and reverse DNA damage and mutagenesis 76). The prevention of DNA damage is important given that it is often an initiating event in carcinogenesis. Research in animal models and in vitro has shown that Triphala is effective in prevention of mutagenesis induced by both chemical- and radiation-induced damage 77). An in vitro study found that Triphala eliminated reactive oxygen species in HeLa cells exposed to ionizing X-radiation or bleomycin, both of which generate DNA strand breaks through the generation of reactive oxygen species 78). In addition, gamma-radiation-induced plasmid DNA strand break was inhibited by Triphala in vitro. The rasayana formulation also inhibited radiation-induced lipid peroxidation in rat liver microsomes and demonstrated the ability to scavenge free radicals such as superoxide. Importantly, the high levels of phenolic compounds such as gallic acid were attributed to the free radical scavenging activity 79).
In animal models, Triphala intervention reduced radiation-induced mortality by 60% in mice fed Triphala for only 7 days before whole-body gamma-irradiation 80). Triphala reversed the increased xanthine oxidoreductase and decreased the superoxide dismutase activity that was observed post-irradiation. Treatment with Triphala also prevented DNA damage in murine white blood cells and spleen cells post-irradiation. Triphala may play a protective role against oxidation, even when administered after exposure.
In addition, other animal studies have reported significantly reduced acute intestinal damage after ionizing radiation exposure in groups fed Triphala (1 kg/g) for at least 5 days before radiation treatment 81). Moreover, studies have demonstrated that Triphala feeding before gamma-radiation exposure reduced radiation sickness and mortality in mice 82). Triphala was reported to scavenge hydroxyl, superoxide anion, and nitric oxide free radicals in a dose-dependent manner in vitro 83). Triphala aqueous extract feeding for 5 days before exposure was also reported as protective against gamma-radiation in mice at a dose of 10 mg/kg, which was 1/28 of the calculated LD50 dose 84). Thus, the antioxidant and free radical scavenging activities of Triphala were concluded to serve a role in its protective effect against ionizing radiation. Human clinical trials to further elucidate the mechanisms of radioprotective action and clinical utility are required.
Anti-tumor activity of Triphala
Triphala has been investigated as a potential antineoplastic agent.61 Numerous studies have been performed in this context and have shown that Triphala exerts an antineoplastic effect on many cancer cell lines, including those of the breast, prostate, colon, and pancreas 85). Data in cell lines show that Triphala has a differential modulatory effect on normal and cancer cell lines. Triphala induces cytotoxicity in cancer cells, which showed increases in intracellular reactive oxygen species, but not normal cells. Excised tumor tissue from Triphala-fed mice compared with controls suggested that apoptosis induction may have mediated reduced tumor growth 86).
Preclinical studies using in vitro and in vivo models report that Triphala inhibits cancer growth in both cell and in vivo models and the effects are mediated through the ERK and p53 pathways 87). In addition, methanol extract of Triphala suppressed proliferation and induced p53-independent apoptosis in human colon cancer stem cells 88). Triphala suppressed the expression of oncogenes, c-Myc and Cyclin D1, and thus Wnt pathway signaling to reduce proliferation and resistance to apoptosis. Triphala-induced apoptotic induction occurred through the intrinsic mitochondrial apoptotic signaling pathway. Moreover, one clinical trial reported that Triphala powder treatment in healthy humans increased cytotoxic T cells and NK cells in the experimental group compared with the control group 89). Thus, Triphala shows potential as an antineoplastic agent and thus should be systematically explored for potential as an adjunct therapy in the management of colon and other cancers.
Antioxidant activity of Triphala and eye health
Antioxidant effects of Triphala have the potential to help maintain eye health. Triphala is a rich source of vitamin C and flavonoids. One study used Triphala as a pretreatment in selenite-induced cataracts in mice. Triphala significantly restored glutathione levels in eye lenses. Triphala also increased the activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase, in the lenses of the experimental group when compared with the control group. While 100% of the mice in the control group developed cataracts, only 20% of the mice pretreated with Triphala developed cataracts. This effect may be linked to the antioxidant activity of Triphala 90).
Anti-inflammatory effects of Triphala
Chronic inflammation is deleterious and affects most major chronic health conditions. Triphala has shown promise as an anti-inflammatory agent. In one study, Triphala performed better or equivalent when compared with standard drug treatment for a variety of biochemical measurements of inflammation.19 In addition, Triphala significantly reduced inflammatory markers as well as bone and cartilage degradation in arthritic rats 91). In this study, Triphala extract was significantly more effective than the nonsteroidal anti-inflammatory drug, indomethacin, in ameliorating arthritic and inflammatory effects. Triphala reduced expression of inflammatory mediators such as IL-17, COX-2, and RANKL through inhibition of NF-κB activation. Another study found that Triphala increased antioxidant levels and decreased lipid peroxidation in the tissues of arthritic rats 92).
In lipopolysaccharide-stimulated macrophages, Triphala treatment suppressed production of inflammatory mediators (such as TNFα, IL-1β, IL-6, MCP-1, VEGF, NO, and PGE2), intracellular free radicals, inflammatory enzymes (such as iNOS and COX-2), and lysosomal enzyme release 93). Chebulagic acid, a constituent in Triphala, was found to inhibit COX and 5-LOX, which are both major enzymes involved in inflammation and carcinogenesis 94). Triphala also increased antioxidant activity in mice after induction of nephrotoxicity from bromobenzene. Triphala ameliorated nephrotoxic effects by upregulating antioxidant enzymes, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase. Lipid peroxidation and markers of kidney dysfunction were reduced in the Triphala-treated group compared with controls 95). The anti-inflammatory effects of Triphala should be investigated in greater detail.
Antiaging effects of Triphala
Triphala extract exerted highly protective antiaging effects on human skin cells in vitro. Triphala extract affects gene expression of human skin cells, stimulating collagen-1 and elastin-synthesizing genes and antioxidant genes responsible for the cellular antioxidant, SOD-2. Triphala extract was found to inhibit melanin production and hyperpigmentation due to the presence of protective phytochemicals. Furthermore, Triphala extract exhibited significant free radical scavenging activity on hydrogen peroxide-induced cell damage and senescence 96). These results demonstrate potential dermal antiaging effects of Triphala, such as increasing collagen and elastin, increasing cellular antioxidants, and decreasing hyperpigmentation.
Triphala and the gut microbiome
It is known that phytochemicals in Triphala such as quercetin and gallic acid promote the growth of Bifidobacteria and Lactobacillus species while inhibiting the growth of undesirable gut residents such as E. coli 97). In addition, the lactic acid bacteria possess enzymatic activity (e.g., tannase) to degrade plant tannins such as gallic acid contained in Triphala 98). For example, Triphala-derived polyphenols such as chebulinic acid are transformed by the human gut microbiota into metabolites such as urolithins, which have the potential to prevent oxidative damage 99). The authors speculate that the bioactivity of Triphala is elicited by the gut microbiome to generate a widened spectrum and abundance of anti-inflammatory compounds.
Triphala-induced benefits in both the elderly and persons of all ages may be enhanced by coadministration of specific probiotic species. Thus, probiotic formulations consisting of bacterial species capable of mediating the increased digestion, bioabsorption, and bioactivity of Triphala may increase and make more uniform the response and impact of Triphala treatment on human populations. Further studies are required to determine the full effect of Triphala on gut microbiota and the potential of specific probiotics to increase the efficacy of the herb.
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