TABLE 4.
Triphala and its constituents with anti-inflammatory properties.
| Herbs | Extracts | Models | Results | References | |
|---|---|---|---|---|---|
| In vitro | In vivo | ||||
| Triphala | Water | Mice | ↓paw edema | (Rasool and Sabina, 2007) | |
| CFA-induced arthritis (extract = 1 g/kg, p.o. for 8 days) | ↓lysosomal enzymes (acid phosphatase, E-glucuronidase, N-acetyl glucosaminidase, and E-galactosidase) in plasma, liver, and spleen | ||||
| Positive control: indomethacin (3 mg/kg, p.o. for 8 days) | ↓protein-bound carbohydrates (hexose, hexosamine, hexuronic acid, fucose, and sialic acid) in liver and spleen | ||||
| ↓marker enzymes (AST, ALT, and ALP) in plasma, liver, and spleen | |||||
| Triphala | Methanol | Rats | ↓paw edema (MAC = 100 mg/kg) | (Prabu et al., 2008) | |
| Carrageenan-induced edema (extract = 100 and 200 mg/kg, p.o. single dose) | ↓wet and dried weight of cotton pellet (MAC = 200 mg/kg) | ||||
| Cotton pellet induced granuloma (extract = 100 and 200 mg/kg, p.o. for 7 days; negative control: 1% tween 80; positive control: indomethacin = 10 mg/kg, p.o. for 7 days) | |||||
| Triphala | Water | Rats | ↓EPP-induced ear edema | (Sireeratawong et al., 2013) | |
| EPP and AA-induced ear edema (extract = 4 mg/ear, topical application; negative control: Mixture of dimethysulfoxide and acetone, 1:1; positive control: phenylbutazone = 1 mg/ear, phenidone = 2 mg/ear) | ↔ AA-induced ear edema | ||||
| Carrageenan-induced paw edema (extract = 300–200 mg/kg, p.o.; negative control: distilled water; positive control: aspirin = 300 mg/kg) | ↓carrageenan-induced paw edema (MAC = 300 mg/kg) | ||||
| Cotton pellet-induced granuloma formation (extract = 1,200 mg/kg, p.o. for 7 days; negative control: distilled water; positive control: aspirin = 300 mg/kg, prednisolone = 5 mg/kg) | ↔ granuloma formation | ||||
| Triphala | Water | Rats | ↓lipid peroxidation, glycoproteins (hexose, hexosamine, and sialic acid), and lysosomal enzymes (acid phosphatase, β-galactosidase, N-acetyl β-glucosaminidase, and cathepsin-D) in paw tissues | (Kalaiselvan and Rasool, 2015) | |
| CFA-induced arthritis (extract = 100 mg/kg, i.p. for 7 days; negative control: saline; positive control: indomethacin = 3 mg/kg, i.p.) | ↑SOD, CAT, GPx, GST, and GSH in paw tissues | ||||
| ↓TNF-α, IL-1β, VEGF, MCP-1, and PGE2 levels in serum and paw tissues | |||||
| Triphala | Distilled water | LPS stimulated RAW 246.7 macrophage (extract = 100–300 μg/ml) | Rats | ↓TNF-α, IL-1β, IL-6, MCP-1, VEGF, NO, PGE2 levels (MAC = 200 μg/ml) | (Kalaiselvan and Rasool, 2016) |
| CFA-induced arthritis extract = 100 mg/kg, i.p. for 7 days; negative control: Saline; positive control: indomethacin = 3 mg/kg, i.p. for 7 days) | ↓lysosomal enzymes [β-galactosidase, N-acetyl β-glucosaminidase, cathepsin-D (MAC = 100 μg/ml), and acid phosphatase (MAC = 300 μg/ml)] | ||||
| ↓TNF-α, IL-1β, IL-6, MCP-1, NF-kBp65, COX-2 and ↑HO mRNA expression (MAC = 200 μg/ml) | |||||
| ↓NF-kBp65 and pNF-kBp65 protein expression (MAC = 200 μg/ml) | |||||
| ↓overexpressed TNF-α, IL-17, iNOS, COX-2 (MAC = 200 μg/ml) | |||||
| ↓free radical formation (MAC = 100 μg/ml) | |||||
| ↓p-NF kB p65, IL-17, COX-2 and RANKL protein expression in paw tissues | |||||
| Triphala (AIE) | Ethanol | TNF-α induced inflammation in retinal choroid microvascular endothelial cells (RF/6 A) (AIE = 1–50 μg/ml, CA, CI and GA = 1–100 μg/ml) | Ex vivo: TNF-α induced angiogenesis in chick chorioallantoic membrane (AlE = 25 μg, CA = 25 μM, CI = 25 μM, GA = 100 μM) | ↓MMP-9 expression (MAC of AIE, CA and CI = 10 μg/ml, GA = 50 μg/ml) | (Shanmuganathan and Angayarkanni, 2018) |
| Chebulagic acid (CA) | In silico docking study: binding to TNF-α-receptor-1 | ↓tube formation, chemotaxis, endothelial cell proliferation (MAC of AIE, CA and CI = 10 μg/ml, GA = 100 μg/ml) | |||
| Chebulinic acid (CI) | ↓IL-6, IL-8, and MCP-1 expression (MAC of AIE = 100 μg/ml, CA and CI = 10 μg/ml, GA = 50 μg/ml) | ||||
| Gallic acid (GA) | ↓phosphorylation of p38, ERK and NF-kB (MAC of AIE, CA and CI = 10 μg/ml, GA = 100 μg/ml) | ||||
| Binding energy of CA = 6.4 kcal/mol, CI = 7.7 kcal/mol, GA = 6.3 kcal/mol | |||||
| ↓angiogenesis (MAC of AIE, CA and CI = 25 μg/ml, GA = 100 μg/ml) | |||||
| P. emblica L | 80% methanol | Rats | ↓serum LDH (MAC = 100 mg/kg) | (Deshmukh et al., 2010) | |
| Acetic acid induced colitis (extract = 100 and 200 mg/kg, p.o. for 7 days; positive control: sulfasalazine = 500 mg/kg, p.o for 3 days) | ↓macroscopic inflammation scores and wet weight of colonic segments (MAC = 200 mg/kg) | ||||
| P. emblica L | Hydroalcohol | Rats | ↓lipid peroxidation in brain (MAC = 300 mg/kg) | (Golechha et al., 2011) | |
| KA-induced seizures (extract = 300, 500, and 700 mg/kg, i.p. for 7 days; negative control: Normal saline, i.p.) | ↑brain GSH levels (MAC = 500 mg/kg) | ||||
| ↓TNF-α in brain (MAC = 300 mg/kg) | |||||
| P. emblica L | 70% ethanol | Rats | Both FPEO and BREO | (Muthuraman et al., 2011) | |
| free (FPEO) and bounded (BREO) phenolic compounds | Carrageenan-induced paw edema (FPEO and BREO = 20 and 40 mg/kg, p.o.; positive control: diclofenac sodium = 12.5 mg/kg, p.o.; negative control: 1% of carboxy methyl cellulose = 1 ml, p.o.) | ↓paw edema (MAC = 40 mg/kg) | |||
| Cotton pellet-induced granuloma formation (extract = 20 and 40 mg/kg, p.o. for 16 days; negative control: 1% of carboxy methyl cellulose = 1 ml, p.o.; positive control: diclofenac = 12.5 mg/kg, p.o.) | ↓granulomatous tissue mass (MAC = 40 mg/kg) | ||||
| ↓lipid peroxidation, myeloperoxidase activity, plasma extravasaion levels and ↑GSH level (MAC = 40 mg/kg) | |||||
| P. emblica L | Commercial fruit extract (patented enzymatic process) | LPS-induced inflammation in HUVEC (extract = 0–100 μg/ml) | Rats | ↓adhesion of THP-1 cells (MAC = 1 μg/ml) | (Pradyumna Rao et al., 2013) |
| LPS-induced endotoxemia (50 mg/kg, p.o.; negative control: PBS = 50 mg/kg, p.o.) | ↓E-selectin mRNA expression (MAC = 30 μg/ml) | ||||
| ↓serum TNF-α and IL-6 levels (MAC = 50 mg/kg) | |||||
| P. emblica L | Hydro-alcohol | Rats | ↓paw edema (MAC = 300 mg/kg) | (Golechha et al., 2014) | |
| Carrageenan (positive control: indomethacin 10 mg/kg, p.o.), histamine (positive control: CPM 3 mg/kg, p.o.), serotonin (positive control: CPH 3 mg/kg, p.o.), and PGE2 (positive control: PBZ 100 mg/kg, p.o.)-induced hind paw edema (extract = 300, 500, and 700 mg/kg, i.p.; negative control: saline = 1 ml/kg, i.p.) | ↑GSH, catalase, and SOD level in paw tissues (MAC = 500 mg/kg) | ||||
| Cotton pellet-induced granuloma formation (extract = 300, 500, and 700 mg/kg, i.p. for 7 days; negative control: Saline = 1 ml/kg, i.p.; positive control: indomethacin = 10 mg/kg, p.o.) | ↓MDA level in paw tissues (MAC = 300 mg/kg) | ||||
| ↓granulomatous tissue mass (MAC = 300 mg/kg) | |||||
| P. emblica L | Methanol | Rats | ↓paw edema (MAC = 200 mg/kg) | (Middha et al., 2015) | |
| Carrageenan-induced paw edema (extract = 200 and 400 mg/kg; positive control: diclofenac = 10 mg/kg) | ↓IL-1β, TNF-α levels (MAC = 200 mg/kg) | ||||
| P. emblica L | Ethyl acetate fraction | Mice | ↓serum TNF-α, IL-1β, IL-6 (MAC = 500 mg/kg) | (Singh et al., 2015) | |
| Arsenic-induced inflammation (extract = 500 mg/kg, p.o. for 30 days; negative control: 2% gum acacia) | Restore T cells and B cells | ||||
| Reverse thymus and spleen weight | |||||
| T. chebula retz | 50% methanol | Rats | ↓joint swelling (MAC = 40 mg/kg) | (Nair et al., 2010) | |
| Formaldehyde-induced arthritis (extract = 20, 40, and 80 mg/kg, p.o. for 10 days) | ↓serum TNF-α (MAC = 40 mg/kg) | ||||
| CFA-induced arthritis (extract = 20, 40, and 80 mg/kg, p.o. for 21 days; positive control: indomethacin = 3 mg/kg) | ↓synovial expression of IL-1β, IL-6, and TNFR1 (maximum at 80 mg/kg) | ||||
| ↓joint swelling (MAC = 20 mg/kg) | |||||
| T. chebula retz | 50% methanol | Rats | ↓paw edema (MAC = 80 mg/kg) | (Nair et al., 2012) | |
| Carrageenan-induced paw edema (extract = 20, 40, and 80 mg/kg, p.o.) | ↓dry granuloma weight (MAC = 40 mg/kg) | ||||
| Cotton pellet-induced granuloma formation (extract = 20, 40, and 80 mg/kg, p.o. for 6 days) | ↓TNF-α, IL-6 and IL-β levels (MAC = 80 mg/kg) | ||||
| CFA-stimulated peritoneal macrophages (extract = 80 mg/kg, p.o. for 6 days; negative control; 1% gum acacia; positive control: indomethacin = 3 mg/kg) | ↓TNF-Rl expression on peritoneal macropharge (MAC = 80 mg/kg) | ||||
| T. chebula retz | 95% ethanol | Mice | ↓ear thickness (MAC = 100 mg/kg) | (Sukakul et al., 2013) | |
| Croton oil-induced ear dermatitis (extract = 100 mg/ml, topical application) | ↓ear plug weight (MAC = 100 mg/kg) | ||||
| T. chebula retz | 70% ethanol | Human RBC stablization method (extract = 50, 100, 250, 500 μg/ml) | Rats | ↓MDA formation (MAC = 50 mg/kg) | (Bag et al., 2013) |
| Carrageenan-induced high paw edema (extract = 50, 100, 250, and 500 mg/kg p.o.; negative control: normal saline; positive control: indomethacin 5 mg/kg, p.o.) | ↓paw edema (MAC = 50 mg/kg) | ||||
| ↑human RBC membrane stability (MAC = 50 μg/ml) | |||||
| T. chebula retz | 80% ethanol | Rats | ↓paw edema (MAC = 300 mg/kg) | (Ibne Jami et al., 2014) | |
| Carrageenan-induced paw edema (extract = 300 mg/kg; negative control: normal saline; positive control: diclofenac 100 mg/kg) | |||||
| T. chebula retz | 100% methanol | LPS-stimulated mouse macrophage cells (RAW 264.7) (compounds = 10, 50 μM; positive control: parthenolide 10 μM, indomethacin 10 μM) | ↓NO production | (Yang et al., 2014) | |
| chebulinic acid (MAC = 50 μM) | |||||
| 2,3,6-tri-O-galloyl-B-d-glucose (MAC = 50 μM) | |||||
| arjunuc acid (MAC = 50 μM) | |||||
| arjulonic acid (MAC = 50 μM) | |||||
| ↓expression of iNOS (MAC = 10 μM) and COX-2 (MAC = 50 μM) | |||||
| T. chebula retz | Water | Rats | ↓EPP-induced ear edema (MAC = 1 mg/ear) | (Sireeratawong et al., 2014) | |
| EPP- and AA-induced ear edema (extract = 1, 2, 4 mg/20 μL/ear; positive control: phenylbutazone, phenidone 1 and 2 mg/ear) | ↔ AA-induced ear edema | ||||
| Carrageenan-induced paw edema (extract = 150, 300, and 600 mg/kg; negative control: normal saline; positive control: Aspirin 300 mg/kg) | ↓paw edema (MAC = 1 mg/kg) | ||||
| Cotton pellet-induced granuloma formation (extract = 600 mg/kg, p.o. for 7 days; positive control: Aspirin 300 mg/kg, prednisolone 5 mg/kg) | ↔ granulomatous tissue mass | ||||
| T. chebula retz | Methanol | Rats | ↓paw edema (MAC = 100 mg/kg) | (Kirubanandan et al., 2015) | |
| Carrageenan-induced paw edema (extract = 100 and 200 mg/kg, p.o.) | ↓granulomatous tissue (MAC = 200 mg/kg) | ||||
| Cotton pellet-induced granuloma formation in rats (extract = 100 and 200 mg/kg, p.o. for 7 days; negative control: 1% Tween80 2 ml/kg, p.o; positive control: indomethacin” 10 mg/kg, p.o.) | |||||
| T. chebula retz | Terminalia chebulanin (polyphenolic compound from fruit) | M5 (a cocktail of IL-1α, IL-17A, IL-22, oncostatin M, and TNFα)-induced HaCaT cells proliferation (extractt = 10 μg/ml) | Mice | ↓TBARS content, ROS production | (An et al., 2016) |
| IMQ-induced psoriatic skin lesion (extract = 50 mg/kg, intragastric; negative control: vehicle vaseline cream) | ↑GSH level (MAC = 10 μg/ml) | ||||
| ↓TNFα, IL-17A, IL-23b, MMP-9, cyclinD, cyclinE mRNA expression (MAC = 10 μg/ml) | |||||
| ↓overexpressed p65 NF-κB expression in tissues and cells (MAC = 10 μg/ml) | |||||
| ↓skin leison through heme oxygenase-I (MAC = 50 mg/kg) | |||||
| ↓TNFα, IL-17 A and IL-23 b levels in serum and skin (MAC = 50 mg/kg) | |||||
| ↑HO-1 expression (MAC = 50 mg/kg) | |||||
| T. chebula retz | Water | Osteoarthritic dogs (extract = 500 mg p.o. bid for 150 days; negative control: placebo capsule) | ↓pain upon limb manipulation significance at 90 days ↓ESR significance at 120 days |
(Murdock, 2015) | |
| T. chebula retz | 70% ethanol | LPS-induced primary microglia cells isolated from mice (extract = 5,10,20,40.80 μg/ml) | ↓TNF-α, IL-1β, IL-6, COX-2, PGE-2, NO concentration (MAC = 20 μg/ml) | (Rahimi et al., 2018) | |
| ↓TNF-α, IL-1β, IL-6, COX-2, iNOS mRNA expression (MAC = 20 μg/ml) | |||||
| ↑Arg-1 mRNA expression (dose dependence) (MAC = 20 μg/ml) | |||||
| ↑urea production (MAC = 40 μg/ml) | |||||
| T. bellirica (gaertn.) roxb | 70% aqueous acetone | Radical scavenging activity | ↓ROS generation in LPS stimulated RAW 264.7 macrophage cells (MAC = 100 μg/ml) | (Jayesh et al., 2018) | |
| LPS-induced macrophage RAW 264.7 cells (extract = 25, 50, 100 μg/ml; positive control: diclofenac sodium) | ↓total COX activity, MPO, total 5-LOX activity (MAC = 25 μg/ml) | ||||
| ↓TNF-α, IL-6 and COX-2 mRNA expression (MAC = 25 μg/ml) | |||||
| ↓ROS production (MAC = 100 μg/ml) | |||||
| T. bellirica (gaertn.) roxb | Water | LPS- or palmitic acid-induced macrophage RAW 264.7 cell (extract = 100, 200, 400 μg/ml; negative control: Distilled water; positive control: GA = 46 μg/kg, EA = 1.6 μg/kg) | LPS-shock model mice (extract = 400 mg/kg, p.o.; negative control: Distilled water) | ↓TNF-α, IL-1β, IL-6, MCP-1, CCL-2, MSR, NOS2 mRNA expression (MAC = 400 μg/ml) | (Tanaka et al., 2018) |
| ↓SR-A protein expression | |||||
| ↓ROS production (MAC = 100 μg/ml) | |||||
| ↓NF-κB nuclear translocation, ↓phosphorylation of NF-κB p65, p38, JNK, and ERK (MAC = 400 μg/ml) | |||||
| Activate Akt/AMPK/Nrf2 pathway (MAC = 100 μg/ml) | |||||
| ↑mRNA expression of antioxidant enzymes (catalase, NQO1, and GCLM) | |||||
| ↓TNF-α and IL-6 mRNA expression | |||||
| Prevent oxidative stress and inflammation in endotoxemic mice | |||||
| T. bellirica (gaertn.) roxb | Ethanol | Rats | ↓paw edema (MAC = 100 mg/kg) | (Chauhan et al., 2018) | |
| Carrageenan-induced paw edema (extract = 100, 200, and 400 mg/kg; negative control: distilled water, positive control: Indomethacin 3 mg/kg) | |||||
ALP, alanine aminotransferase; ALT, alkaline phosphatase; AA, arachidonic acid; AST, aspartate aminotransferase; CCL-2, C-C motif chemokine ligand 2 gene; CPM, chlorpheniramine; SR-A, class A scavenger receptor A; CFA, complete Freund’s adjuvant; CPH, cyproheptadine; ESR, erythrocyte sedimentation rate; GCLM, glutamate-cysteine ligase modifier subunit; HUVEC, human umbilical vein endothelial cells; IMQ, imiquimod; KA, kainic acid; MSR, macrophage scavenger receptor gene; MPO, myeloperoxidase; NQO1, NADPH quinone oxidoreductase 1; PBZ, phenylbutazone; RANKL, receptor activator of nuclear kappa-B ligand; TBARS, thiobarbituric acid reactive substances; vWF, von Willebrand factor.