Panchvalkala, a traditional Ayurvedic formulation, exhibits antineoplastic and immunomodulatory activity in cervical cancer cells and C57BL/6 mouse papilloma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Panchvalkala, an Ayurvedic traditional formulation has references in Charak Samhita and Bhavaprakasha Nighantu for the treatment of women with endometriosis-related problems, leucorrhea and vaginal ailments. The formulation comprises of equal ratios of the barks from Ficus glomerata, Ficus virens, Ficus religiosa, Ficus benghalensis, and Thespesia populnea. AIM OF THE STUDY: The present study aimed to evaluate the anticancer and immunomodulatory activity of aqueous extract of Panchvalkala (PVaq) against cervical cancer in vitro and in vivo. MATERIALS AND METHODS: The effect of PVaq on disruption of mitochondrial membrane potential in cervical cancer cell lines, SiHa and HeLa, was studied by using JC1 dye. The expression of generic caspases in the cells after treatment with PVaq was evaluated by ELISA kit. The expression of pRb, p53, E6 and E7 proteins were evaluated by western blotting. Acute oral toxicity and DRF studies were performed in Swiss albino mice by following OECD guidelines 423 and 407, respectively. Tumor retardation study was done in C57BL/6 mouse papilloma model. The mice were divided into six groups: No tumor control (NTC), Tumor control (TC), Cisplatin (Cis) (4 mg/kg b.w.), PVaq 100, 200 mg/kg b.w and combination of PVaq (200 mg/kg b.w.) and Cisplatin (4 mg/kg b.w.). The mice were orally gavaged with PVaq daily for 14 days and cisplatin was given intravenously on every 1st, 5th and 9th day. Hematological and biochemical parameters were studied by using hematology analyzer and kits, respectively. E6 and E7 gene expression in the tumor samples was determined by qPCR. Th1 and Th2 cytokine levels were determined by ELISA. RESULTS: PVaq induced mitochondrial depolarization in SiHa and HeLa, and increased the expression of generic caspases, resulting into apoptosis. PVaq upregulated the expression of tumor suppressor proteins (p53 and pRb) and reduced the expression of viral oncoproteins (E6 and E7). Acute toxicity study displayed non-toxicity of PVaq while DRF study ensured its safe dose for further efficacy studies. PVaq reduced tumor volume and weight in mouse papilloma model and induced immunomodulation in the animals. It increased serum levels of IL-2 (Th1) with a concomitant decrease in IL-10 (Th2) cytokines. The drug did not affect body weight, food consumption and organ histopathology of the animals. CONCLUSIONS: PVaq exhibited anticancer and immunomodulatory activities against cervical cancer cells and female mouse papilloma model.

Matairesinol, an active constituent of HC9 polyherbal formulation, exhibits HDAC8 inhibitory and anticancer activity.

Histone deacetylase 8 (HDAC8) has emerged as a promising drug target for cancer therapeutics development. HDAC8 has been reported to regulate cancer cell proliferation, invasion and promote metastasis through modulation of cell cycle associated proteins. Of late, phytocompounds have been demonstrated to exhibit anticancer and anti-HDAC8 activity. Here, we have shown the HDAC8 inhibitory potential of an active phytocompound from HC9 (herbal composition-9), a polyherbal anticancer formulation based on the traditional Ayurvedic drug, Stanya Shodhan Kashaya. HC9 was recently reported to exhibit anticancer activity against breast cancer cells through induction of cell cycle arrest, decrease in migration and invasion as well as regulation of inflammation and chromatin modulators. In silico studies such as molecular docking, molecular dynamics (MD) simulation and binding free energy analyses showed greater binding energy values and interaction stability of MA with HDAC8 compared to other phytocompounds of HC9. Interestingly, in vitro validation confirmed the anti-HDAC8 activity of MA. Further, in vitro studies showed that MA significantly decreased the viability of breast and prostate cancer cell lines, thereby confirming its anticancer potential.