Safety of the Oral Triphala Recipe from Acute and Chronic Toxicity Tests in Sprague-Dawley Rats

Background: The Indian Ayurvedic herbal formula Triphala (TPL) is known for its pharmacological properties for immunomodulation, anti-inflammation, antioxidant, and anti-cancer. This study aimed to investigate the acute and chronic toxicities of the Triphala recipe in a rat model. Methods: To assess the acute toxicities, 5000 mg/kg of TPL was orally administered to Sprague-Dawley rats. For chronic toxicities, different dose levels of TPL at 600, 1200, and 2400 mg/kg/day were given daily for 270 days. General health and behaviors and the body and organ weights of the rats were monitored. At the end of the experiment, blood samples were evaluated for hematology and biochemistry profiles. The evaluation of the internal organs’ appurtenance and necropsy was performed to confirm the tissue histopathology. Results: The results showed that there was no sign of acute toxicity in the TPL group with a decrease in sex organ weights. No significant differences in the rats’ behaviors, physical health, body, or organ weights were found between the controls and the rats receiving the 270/day of oral Triphala at 600, 1200, and 2400 mg/kg/day. However, some alterations in blood chemistries and hematology, including glucose, BUN, red blood cells, Hb, HCT, and MCV, were observed without abnormalities in histopathology. Conclusions: It has been demonstrated that the long-term use of TPL in rat models is safe. No toxic effects were found, suggesting possible safety for long-term use in humans

<i>Ficus dubia</i> Latex Extract Induces Cell Cycle Arrest and Apoptosis by Regulating the NF-κB Pathway in Inflammatory Human Colorectal Cancer Cell Lines

Colorectal cancer is one of the most diagnosed cancers that is associated with inflammation. Ficus dubia latex is recognized as a remedy with various therapeutic effects in traditional medicine, including anti-inflammatory and antioxidant activity. The present study aims to compare the anti-tumor activity of Ficus dubia latex extract (FDLE) against HCT-116 and HT-29 human colorectal cancer cell lines in normal and inflammatory condition and explore its mechanism of action. FDLE exhibited remarkable antiproliferative activity against HCT-116 and HT-29 colorectal cancer cell lines in both conditions using MTT and colony formation assays and more effective anti-proliferation was observed in inflammatory condition. Mechanistically, FDLE induced cell cycle arrest at G0/G1 phase by down-regulating NF-κB, cyclin D1, CDK4 and up-regulatingp21 in both cell in normal condition. In inflammatory condition, FDLE not only exhibited stronger induction of cell cycle arrest in both cells by down-regulating NF-κB, cyclin D1, CDK4 and down-regulating p21, but also selectively induced apoptosis in HCT-116 cells by down-regulating NF-κB and Bcl-xl and up-regulating Bid, Bak, cleaved caspase-7 and caspase-3 through stronger ability to regulate these proteins. Our results demonstrated that the phytochemical agent in the latex of Ficus dubia could potential be used for treatment and prevention of human colorectal cancer, especially in inflammation-induced hyperproliferation progression