Anti-Stress and Glial Differentiation Effects of a Novel Combination of Cucurbitacin B and Withanone (CucWi-N): Experimental Evidence

Abstract

Background: Natural extracts and compounds used in traditional home medicine are known for their safety and a variety of health promoting and therapeutic potentials. In contrast to the single molecule mediated targets, the combinational therapies are preferred for their multi-functional and limited toxic regimens and may be useful for disease therapeutics as well as to increase the quality of life during a variety of environmental stresses. Purpose: We aimed to combine the active ingredients of Chinese (Helicteres angustifolia) and Indian (Withania somnifera) ginsengs to develop a natural, efficient, and welfare combinatorial mixture with high anti-stress and glial differentiation potentials. Methods: Using cultured cells as a model system, we developed a combination of active ingredients of Chinese (Cucurbitacin B [Cuc]) and Indian (Withanone [Wi-N]) ginsengs. Eleven chemical models of environmental stresses were used. Cytotoxicity studies were performed using human skin fibroblast for anti-stress and rat glioma cells for glial differentiation effects. Results: We demonstrate that the novel combination of Cuc and Wi-N, CucWi-N, was non-toxic to normal cells. It caused stress protection in assays using normal human fibroblasts subjected to a variety of stresses. Of note, cells showed remarkable protection against oxidative and UV stresses and marked by decrease in DNA damage and reactive oxygen species. We examined and found the glial differentiation potential of CucWi-N in rat glioblastoma cells. CucWi-N clearly induced differentiation phenotype, well-marked with upregulation of GAP43, MAP2, and GFAP, which have been shown to play a key role in glial differentiation. Conclusion: These data demonstrate anti-stress and glial differentiation potential of CucWi-N (a novel combination of Cuc and Wi-N) that could be recruited in nutraceutical and pharmaceutical avenues and hence warrant further evaluation and mechanistic studies.

Cucurbitacin B as a Chinese Medicine Monomer Inhibits Cell Proliferation, Invasion, and Migration in Nasopharyngeal Carcinoma

“…Previous studies have shown that there is no obvious toxicity to normal cells at CuB concentrations lower than 5-10 μM [16]. Wakimoto et al showed that when nude mice transplanted with MD-MB-231 tumor cells were injected with CuB (1 mg/kg) intraperitoneally for 6 weeks, the tumor volume reduced by 55% compared to the control group while body weight did not reduce [17].…”

Anti-Stress, Glial- and Neuro-Differentiation Potential of Resveratrol: Characterization by Cellular, Biochemical and Imaging Assays

“…It has been established that the brain functions deteriorate with prolonged exposure to a variety of stresses [12]. Brain-derived cells in culture have been established as a reliable model to study the molecular mechanism of stress-induced damage and its prevention/recovery by natural and synthetic reagents [5,15,39]. In these premises, we used C6 cells in conjunction with a variety of stress models including oxidative stress, smoke, hypoxia, heat-stress, metal and emotional stress to investigate the anti-stress potential of resveratrol.…”

“…Several molecules have been suggested for this purpose. We previously showed the potential of natural compounds like the marine carotenoids and cucurbitacin B-withanone cocktail to induce astrocytic morphology and mixed type biochemical differentiation in rat glioma cells [5,15]. Proteins with the most remarkable changes included GFAP (indicating astrocytic differentiation) and MAP2 (indicating neuronal differentiation).…”

Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors

“…In modern scientific approaches, it exerted neuroprotection against Alzheimer's disease models and anti-inflammatory effects in brain cells [21,22]. In combination with cucurbitacin B, WN protected from oxidative stress by lowering antioxidants [23]. Hence, WN may be a powerful substance whose antidepressant and stress-reducing effects should be further investigated.…”