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Cell protective effects of Haritaki

Terminalia Chebula: Cell protection

Scientific experiments and studies that underline the cell protective effects of Haritaki.

Several studies have confirmed a protective effect of Haritaki plant extract against cellular damage. Furthermore, a protective effect against endothelial cell dysfunction was found.

Cytoprotective role of the aqueous extract of Terminalia chebula on renal epithelial cells

International Braz J Urol (official journal of the Brazilian society of Urology) Mar-Apr 2012;38(2):204-13; discussion 213-4. doi: 10.1590/s1677-55382012000200008.

The antilithiatic activity of Terminalia chebula was investigated on nucleation and growth of the calcium oxalate crystals. The protective potency of the plant extract was also tested on oxalate induced cell injury of both NRK-52E and MDCK renal epithelial cells. Results: The percentage inhibition of CaOx nucleation was found 95.84 % at 25µg/mL of Terminalia chebula aqueous extract which remained almost constant with the increasing concentration of the plant extract; however, plant extract inhibited CaOx crystal growth in a dose dependent pattern. When MDCK and NRK-52E cells were injured by exposure to oxalate for 48 hours, the aqueous extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant extract, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. Conclusion: Our study indicates that Terminalia chebula is a potential candidate for phytotherapy against urolithiasis as it not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role.

[Link to the scientific study]

Inhibitory effects of Terminalia chebula extract on glycation and endothelial cell adhesion

Planta Medica 2011 Jul;77(10):1060-7. doi: 10.1055/s-0030-1270748. Epub 2011 Feb 9.

Terminalia chebula Retz. has been used in India for a long time to treat many diseases, and its extract was reported to have antidiabetic activity in vivo. In this study, T. chebula methanolic extract (TCE) containing 2.7 % chebulic acid was evaluated for its preventive effects against the formation of advanced glycation end products (AGEs) and endothelial cell dysfunction. When the effects of TCE on AGE formation and on protein crossing-linking by glycation with D-threose and lens crystallines were examined, TCE showed inhibitory activity in a dose-dependent manner, and the concentration of 1000 µg/mL presented an activity similar to that of 5 mM aminoguanidine as a positive control. Upon investigating the protective activity of TCE against AGE-induced vascular endothelium dysfunction, human umbilical vein endothelial cells (HUVEC) incubated with 100 µg/mL of AGEs had significantly enhanced reactive oxygen species (ROS) formation, whereas the treatment of T. chebula reduced AGE-induced ROS generation. The incubation of HUVEC with 100 µg/mL of AGEs caused a considerable increase in THP-1 monocytic cell adhesion, but this adhesion was reduced by the treatment of TCE. These results suggest that TCE is a potential agent for alleviating diabetic complications.

[Link to the scientific study]

In vitro and in vivo antiplasmodial activity and cytotoxicity of water extracts of Phyllanthus emblica, Terminalia chebula, and Terminalia bellerica

Journal of the Medical Association of Thailand 2010 Dec;93 Suppl 7:S120-6.

Objective: To evaluate the in vitro and in vivo antiplasmodial activity and the cytotoxicity of Phyllanthus emblica Linn, Terminalia chebula Retz, and Terminalia bellerica (Gaertn) Roxb extracts. Material and method: Standard phytochemical screening tests were used to detect metabolites in the plant extract. The water extracts of medicinal plants were tested for their antiplasmodial activity in vitro by assessing their ability to inhibit the uptake of [3H] hypoxanthine into the Plasmodium falciparum K1 multidrug-resistant strain. Cytotoxicity of all extracts was determined on Vero cell line. The in vivo antiplasmodial activity in Plasmodium berghei infected mice was evaluated by the standard 4-day suppressive test. Results: Phytochemical screening of the water extracts of three plants revealed the presence of flavonoids, hydrolysable tannins, saponin and terpenes. All plant extracts showed antimalarial activity (IC50 values ranging from 14.33 +/- 0.25-15.41 +/- 0.61 microg/ml). The water extract of Terminalia bellerica (Gaertn) Roxb had the highest in vitro antiplasmodial activity followed by Phyllanthus emblica Linn. and Terminalia chebula Retz. The cytotoxic activity was exhibited by all plant extracts on Vero cells with IC50 values of 157.86 to 238.70 mg/ml. All of the plant extracts showed selectivity with the selectivity index (SI) ranged from 11 to 17. A standard 4-day suppressive test on P. berghei infected mice was used to evaluate the in vivo antiplasmodial activity of the extracts at 250 mg/kg/day. The results revealed that in vivo antiplasmodial activity with good suppression activity ranged from 53.40% to 69.46%. Conclusion: All of the plant extracts exhibited interesting in vitro and in vivo antiplasmodial activity with good selectivity.

[Link to the scientific study]

In vitro and in vivo antiplasmodial activity and cytotoxicity of water extracts of Phyllanthus emblica, Terminalia chebula, and Terminalia bellerica

Journal of the Medical Association of Thailand 2010 Dec;93 Suppl 7:S120-6.

Objective: To evaluate the in vitro and in vivo antiplasmodial activity and the cytotoxicity of Phyllanthus emblica Linn, Terminalia chebula Retz, and Terminalia bellerica (Gaertn) Roxb extracts. Material and method: Standard phytochemical screening tests were used to detect metabolites in the plant extract. The water extracts of medicinal plants were tested for their antiplasmodial activity in vitro by assessing their ability to inhibit the uptake of [3H] hypoxanthine into the Plasmodium falciparum K1 multidrug-resistant strain. Cytotoxicity of all extracts was determined on Vero cell line. The in vivo antiplasmodial activity in Plasmodium berghei infected mice was evaluated by the standard 4-day suppressive test. Results: Phytochemical screening of the water extracts of three plants revealed the presence of flavonoids, hydrolysable tannins, saponin and terpenes. All plant extracts showed antimalarial activity (IC50 values ranging from 14.33 +/- 0.25-15.41 +/- 0.61 microg/ml). The water extract of Terminalia bellerica (Gaertn) Roxb had the highest in vitro antiplasmodial activity followed by Phyllanthus emblica Linn. and Terminalia chebula Retz. The cytotoxic activity was exhibited by all plant extracts on Vero cells with IC50 values of 157.86 to 238.70 mg/ml. All of the plant extracts showed selectivity with the selectivity index (SI) ranged from 11 to 17. A standard 4-day suppressive test on P. berghei infected mice was used to evaluate the in vivo antiplasmodial activity of the extracts at 250 mg/kg/day. The results revealed that in vivo antiplasmodial activity with good suppression activity ranged from 53.40% to 69.46%. Conclusion: All of the plant extracts exhibited interesting in vitro and in vivo antiplasmodial activity with good selectivity.

[Link to the scientific study]

Mutagenicity and oral toxicity studies of Terminalia chebula

Phytotherapy Research 2012 Jan;26(1):39-47. doi: 10.1002/ptr.3504. Epub 2011 May 2.

The fruit of Terminalia chebula Retz. (T. chebula), which is a member of the Combfreetaceae family, is used widely in Asian countries as a traditional folk medicine, and its extract has been reported to be an anticancer, antidiabetic and anticaries agent. In our previous study, chebulic acid isolated from T. chebula extract was confirmed to show antioxidant activity and protective action against endothelial cell dysfunction. In order to support the safety-in-use of the ethyl acetate (EtOAc)-soluble portion of a T. chebula ethanol extract containing 29.4% chebulic acid content, the prepared portion was tested in an in vitro mutagenicity assay, and a single- and 14-day repeated dose oral toxicity study. In the bacterial mutation assay, up to 5000 µg/mL concentration of the EtOAc-soluble portion, the numbers of colonies did not increase whether with or without metabolic activation. In the oral toxicity study, the single oral dose of the extract at 2000 mg/kg did not produce mortality or abnormal lesions in the internal organs of rats. The results of a 14-day orally repeated dose showed that the EtOAc-soluble portion of T. chebula ethanol extracts gave no adverse effects at dosages of 2000 mg/kg in rats in the study.

[Link to the scientific study]

Terminalia Chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation

Scientific Repors 2016 Apr 27;6:25094. doi: 10.1038/srep25094.

Death receptor (DR) ligation elicits two different modes of cell death (necroptosis and apoptosis) depending on the cellular context. By screening a plant extract library from cells undergoing necroptosis or apoptosis, we identified a water extract of Terminalia chebula (WETC) as a novel and potent dual inhibitor of DR-mediated cell death. Investigation of the underlying mechanisms of its anti-necroptotic and anti-apoptotic action revealed that WETC or its constituents (e.g., gallic acid) protected against tumor necrosis factor-induced necroptosis via the suppression of TNF-induced ROS without affecting the upstream signaling events. Surprisingly, WETC also provided protection against DR-mediated apoptosis by inhibition of the caspase cascade. Furthermore, it activated the autophagy pathway via suppression of mTOR. Of the WETC constituents, punicalagin and geraniin appeared to possess the most potent anti-apoptotic and autophagy activation effect. Importantly, blockage of autophagy with pharmacological inhibitors or genetic silencing of Atg5 selectively abolished the anti-apoptotic function of WETC. These results suggest that WETC protects against dual modes of cell death upon DR ligation. Therefore, WETC might serve as a potential treatment for diseases characterized by aberrantly sensitized apoptotic or non-apoptotic signaling cascades.

[Link to the scientific study]


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