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Beneficial effects of Haritaki in cancer

Terminalia Chebula: Cancer

Scientific experiments and studies on the beneficial effects of Haritaki in cancer.

In the studies, the anti-cancer activity of homeopathic preparations of Haritaki against breast cancer and shows its nanoparticulate nature.

The effective cytotoxic activity of Haritaki is attributed to its high concentration of phenols/flavonoids present.

Since oxidative stress promotes the development of cancer, the antioxidant property of the plant extract shows its use in cancer treatment.

Terminalia chebula extract acts as a potential NF-?B inhibitor in human lymphoblastic T cells

Phytotherapy Research 2017 Dec;31(12):1849-1857. doi: 10.1002/ptr.5927. Epub 2017 Sep 18.

Chebulinic acid, an ellagitannin found in the fruits of Terminalia chebula, has been extensively used in traditional Indian system of medicine. It has shown to have various biological activities including antitumor activity. The present study aims to investigate the cytotoxic potential of chebulinic acid in human myeloid leukemia cells. Interestingly, chebulinic acid caused apoptosis of acute promyelocytic leukemia HL-60 and NB4 cells but not K562 cells. In vitro antitumor effects of chebulinic acid were investigated by using various acute myeloid leukemia cell lines. Chebulinic acid treatment to HL-60 and NB4 cells induced caspase activation, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, chromatin condensation, and changes in the mitochondrial membrane permeability. Additionally, inhibition of caspase activation drastically reduced the chebulinic acid-induced apoptosis of acute promyelocytic leukemia cells. Our data also demonstrate that chebulinic acid-induced apoptosis in HL-60 and NB4 cells involves activation of extracellular signal-regulated kinases, which, when inhibited with ERK inhibitor PD98059, mitigates the chebulinic acid-induced apoptosis. Taken together, our findings exhibit the selective potentiation of chebulinic acid-induced apoptosis in acute promyelocytic leukemia cells.

[Link to the scientific study]

Anti-secretory and cyto-protective effects of chebulinic acid isolated from the fruits of Terminalia chebula on gastric ulcers

Phytomedicine 2013 Apr 15;20(6):506-11. doi: 10.1016/j.phymed.2013.01.002. Epub 2013 Feb 23.

In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated. Chebulinic acid was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of chebulinic acid was observed against CRU (62.9%), AS (55.3%), AL (80.67%) and PL (66.63%) induced ulcer models. The reference drug omeprazole (10 mg/kg, p.o.) showed 77.73% protection against CRU, 58.30% against AS and 70.80% against PL model. Sucralfate, another reference drug (500 mg/kg, p.o.) showed 65.67% protection in AL induced ulcer model. Chebulinic acid significantly reduced free acidity (48.82%), total acidity (38.29%) and upregulated mucin secretion by 59.75% respectively. Further, chebulinic acid significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 65.01 µg/ml as compared to the IC50 value of omeprazole (30.24 µg/ml) confirming its anti-secretory activity.

[Link to the scientific study]

Combined Zingiber officinale and Terminalia chebula Induces Apoptosis and Modulates mTOR and hTERT Gene Expressions in MCF-7 Cell Line

Nutrition and Cancer 2021;73(7):1207-1216. doi: 10.1080/01635581.2020.1792518. Epub 2020 Jul 14.

In this study, we evaluated the cytotoxicity and apoptotic activity of Zingiber officinale (ZO), Terminalia chebula (TC) alone, and in combination (ZO:TC-1:4). The presence of major bioactive compounds in ZO (6-gingerol and 6-shogaol) and TC (gallic acid, ellagic acid, and chebulinic acid) were evaluated by high performance liquid chromatography. The IC50 values of ZO, TC, and ZOTC (1:4) was estimated to be 88.5, 108.5, and 53.5 µg/mL, respectively. The cell death and cytomorphology changes upon treatment were observed. At these concentrations, ZO, TC, and ZOTC showed reduced mitochondrial membrane potential, increased reactive oxygen species, and apoptotic activities. It was also reported to downregulate mTOR and hTERT gene expression levels which are the primary genes for cell proliferation and growth. This first report on ZOTC combination has the potential to develop as a therapeutic agent for breast cancer.

[Link to the scientific study]

Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): characterization, quantitation and determination of antioxidant capacities

Phytochemistry 2010 Jul;71(10):1132-48. doi: 10.1016/j.phytochem.2010.03.018. Epub 2010 May 6.

Thirty-four polyphenolic substances in methanol extracts of the fruits of Terminalia bellerica, Terminalia chebula and Terminalia horrida, three plants used in Egyptian folk medicine, were initially identified by HPLC-ESI-MS and quantitated by analytical HPLC after column chromatography on Sephadex LH-20. After purification by semi-preparative HPLC the compounds were identified by their mass and fragmentation patterns using ESI-MS-MS. For several compounds detailed 1H/13C NMR analysis at 600 MHz was performed. Two polyphenolics, namely 4-O-(4''-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid and 4-O-(3'',4''-di-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid were identified by NMR. Antioxidant capacities of the raw fruit extracts and the major isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), oxygen radical absorbance capacity (ORAC) and ferric reducing ability of plasma (FRAP) in vitro assays and indicated that chebulic ellagitannins have high activity which may correlate with high potential as cancer chemopreventive agents. Therefore, further studies (metabolism, bioavailability and toxicity) of the polyphenolics in Terminalia species using preclinical models and in vivo human intervention trials are warranted.

[Link to the scientific study]

Evaluating the anticancer activity and nanoparticulate nature of homeopathic preparations of Terminalia chebula

Homeopathy 2016 Nov;105(4):318-326. doi: 10.1016/j.homp.2016.02.004. Epub 2016 Apr 12.

Background: Breast cancer is the most common cancer diagnosed among women and is the second leading cause of cancer death. Homeopathic medicines are part of the alternative medicines that are given as a supportive therapy in breast cancer. The objective of this study was to investigate the anticancer activity of commercially available homeopathic preparations of Terminalia chebula (TC) and evaluate their nanoparticulate nature. Methods: Mother tincture (MT) and other homeopathic preparations (3X, 6C and 30C) of TC were tested for their effect on the viability of breast cancer (MDAMB231 and MCF7) and non-cancerous (HEK 293) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell growth assay was performed to analyze the effect of the different potencies on the growth kinetics of breast cancer cells. MT and 6C were evaluated for the presence of nanoparticles by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: MT decreased the viability of breast cancer (MDAMB231 and MCF7) and non-cancerous (HEK 293) cells. However, the other potencies (3X, 6C and 30C) decreased the viability of only breast cancer cells without affecting the viability of the non-cancerous cells. All the potencies, MT, 3X, 6C and 30C, reduced growth kinetics of breast cancer cells, more specifically at 1:10 dilution at 24, 48 and 72 h. Under SEM, MT appeared as a mesh-like structure whereas under TEM, it showed presence of nanoclusters. On the other hand, 6C potency contained 20 nm sized nanoparticles. Conclusion: The current study reports the anticancer activity of homeopathic preparations of TC against breast cancer and reveals their nanoparticulate nature. These preliminary results warrant further mechanistic studies at both in vitro and in vivo levels to evaluate the potential of TC as nanomedicine in breast cancer.

All the potencies, MT, 3X, 6C and 30C, reduced growth kinetics of breast cancer cells.

[Link to the scientific study]

Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit

Journal of Ethnopharmacology 2002 Aug;81(3):327-36. doi: 10.1016/s0378-8741(02)00099-5.

A 70% methanol extract of Terminalia chebula fruit, was studied for its effects on growth in several malignant cell lines including a human (MCF-7) and mouse (S115) breast cancer cell line, a human osteosarcoma cell line (HOS-1), a human prostate cancer cell line (PC-3) and a non-tumorigenic, immortalized human prostate cell line (PNT1A) using assays for proliferation ([(3)H]-thymidine incorporation and coulter counting), cell viability (ATP determination) and cell death (flow cytometry and Hoechst DNA staining). In all cell lines studied, the extract decreased cell viability, inhibited cell proliferation, and induced cell death in a dose dependent manner. Flow cytometry and other analyses showed that some apoptosis was induced by the extract at lower concentrations, but at higher concentrations, necrosis was the major mechanism of cell death. ATP assay guided chromatographic fractionation of the extract yielded ellagic acid, 2,4-chebulyl-beta-D-glucopyranose (a new natural product), and chebulinic acid which were tested by ATP assay on HOS-1 cell line in comparison to three known antigrowth phenolics of Terminalia, gallic acid, ethyl gallate, luteolin, and tannic acid. Chebulinic acid (IC(50) = 53.2 microM +/- 0.16) > tannic acid (IC(50) = 59.0 microg/ml +/- 0.19) > and ellagic acid (IC(50) = 78.5 microM +/- 0.24), were the most growth inhibitory phenolics of T. chebula fruit in our study.

[Link to the scientific study]

Biological activities of phenolic compounds and triterpenoids from the galls of Terminalia chebula

Chemistry & Biodiversity 2013 Aug;10(8):1448-63. doi: 10.1002/cbdv.201300149.

Plants have been an important source for discovery of anticancer compounds. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicines; therefore the anticancer efficacy of many plants that are used in traditional medicine is yet to be verified. The objective of the study was to evaluate the cytotoxic potential of ethanolic leaf gall extract of Terminalia chebula are evaluated against buffalo rat liver 3A, MCF-7 (Human mammary gland adenocarcinoma) and A-549 (Human lung cancer) cell lines. The cytotoxic effect of the ethanolic extract was evaluated by MTT assay. The extract was potent and effective in inducing cytotoxic effects in all the cell lines with an IC50 value of 305.18 ± 1.7 μg/mL, 643.13 ± 4.2 μg/mL, and 208.16 ± 3.7 μ/mL, respectively. The extract was more effective against A549 cell lines when compared to others. The presences of phenolics, triterpenoids, and flavonoids were identified in the extract. The extract showed total phenolic and flavonoid content of 478 ± 2.2 mg of gallic acid equivalent/g d.w and 538 ± 1.4 mg of quercetinequivalent/g d.w, respectively. This higher content of total phenolics and flavonoids found in the ethanolic extract was directly associated to higher cytotoxicity activity.

Conclusion

The ethanolic leaf gall extract of T. chebula showed effective cytotoxic activities; which might be attributed to the phenolics/flavonoids present in higher concentration. Future work will be interesting to know the chemical composition of the extract and also better understand the mechanism of action of the constituents present in the extract to develop it as drug for therapeutic application.

[Link to the scientific study]

Exploration of anti-breast cancer effects of Terminalia chebula extract on DMBA-induced mammary carcinoma in Sprague Dawley rats

Future Journal of Pharmaceutical Sciences volume 6, Article number: 108 (2020)

Background

Plant extracts are effectively acting as the natural medicinal cocktail, non-side effective, efficacious, and freely available. The present study aimed to unveil the pharmacological and medicinal effects of Terminalia chebula plant extract in 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Sprague Dawley rats. The plant extract obtained was subjected to in vivo antioxidant and anticancer studies in various concentrations after an analytical technique such as FTIR, GCMS, and HPLC-based chemo-profiling in Sprague Dawley rats.

Results

Apart from the antiproliferative effect on breast cancer cell line (MCF-7) and normal breast epithelial cells (MCF-10a), we have measured the changes in body weight, along with other tumor parameters such as tumor volume, tumor incidence, tumor weight, tumor burden, serum biochemical parameters, and histopathological findings of breast tissue. As the oxidative stress further enhances the development of cancer, the antioxidant property of the plant extract demonstrates its use against cancer treatment. One hundred fifty milligrams per milliliter (IC50 250 μg/mL) concentration of the ethanolic extract was vital for the proliferation of MCF-7 cell lines (Fig. 7a). Meanwhile, 300 μg/mL (IC50 150 μg/mL) was an effective dose to attain a maximum HDAC inhibition of 78%. Also, the normal liver and kidney functioning revealed the non-toxicity nature of the plant.

Conclusion

Terminalia chebula could be one of the effective naturally obtained anti-breast cancer medications. Isolation and characterization of individual bioactive compounds of T. chebula would be the future perspective.

[Link to the scientific study]

Aqueous Extract of Terminalia chebula Induces Apoptosis in Lung Cancer Cells Via a Mechanism Involving Mitochondria-mediated Pathways

Human and Animal Health • Braz. arch. biol. technol. 58 (2) • Mar-Apr 2015

The current study was designed to evaluate the aqueous extract of Terminalia chebula activity, and the main pathway was detected on lung cancer by extracts of T. chebula. Aqueous extract of T. chebula was separated using a zeolite, and five fractions of T. chebula extract were obtained and analyzed by ultraviolet (UV) and infrared (IR) spectroscopy. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods against human lung cancer (A549) and mouse lung cancer cell line LLC. T. chebula acts by regulating the Bcl-2 family protein-mediated mitochondrial pathway detected by western blot. Fraction 4 of the T. chebula extract showed much function and was thus studied further. Fraction 4 increased the activation of caspase-3, induced PARP cleavage, and promoted cytochrome c release into the cytoplasm. These data suggest that T. chebula acts by regulating the Bcl-2 family protein-mediated mitochondrial pathway and provide evidence that T. chebula deserves further investigation as a natural agent for treating and preventing cancer.

[Link to the scientific study]


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