hispidin and 5-6-dehydrokawain

PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic kinase, and a number of herbal PAK1-blockers such as propolis and curcumin have been shown to be anti-oncogenic and anti-melanogenic as well as anti-alopecia (promoting hair growth). Previously, we found several distinct PAK1-inhibitors in Okinawa plants including Alpinia zerumbet (alpinia). Thus, here, we tested the effects of these herbal compounds and their derivatives on the growth of cancer or normal hair cells, and melanogenesis in cell culture of A549 lung cancer, hair follicle dermal papilla cell, and B16F10 melanoma. Among these herbal PAK1-inhibitors, cucurbitacin I from bitter melon (Goya) turned out to be the most potent to inhibit the growth of human lung cancer cells with the IC50 around 140 nM and to promote the growth of hair cells with the effective dose around 10 nM. Hispidin, a metabolite of 5,6-dehydrokawain from alpinia, inhibited the growth of cancer cells with the IC50 of 25 μM as does artepillin C, the major anti-cancer ingredient in Brazilian green propolis. Mimosine tetrapeptides (MFWY, MFYY, and MFFY) and hispidin derivatives (H1-3) also exhibited a strong anti-cancer activity with the IC50 ranging from 16 to 30 μM. Mimosine tetrapeptides and hispidin derivatives strongly suppressed the melanogenesis in melanoma cells.

Topics: Alpinia; Animals; Brazil; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Hair Follicle; Humans; Lim Kinases; Melanins; Melanoma, Experimental; Mice; Momordica charantia; p21-Activated Kinases; Phenylpropionates; Pyrones; Triterpenes

Obesity and its related disorders have become leading metabolic diseases. In the present study, we used 3T3-L1 adipocytes to investigate the anti-obesity activity of hispidin and two related compounds that were isolated from Alpinia zerumbet (alpinia) rhizomes. The results showed that hispidin, dihydro-5,6-dehydrokawain (DDK), and 5,6-dehydrokawain (DK) have promising anti-obesity properties. In particular, all three compounds significantly increased intracellular cyclic adenosine monophosphate (cAMP) concentrations by 81.2% ± 0.06%, 67.0% ± 1.62%, and 56.9% ± 0.19%, respectively. Hispidin also stimulated glycerol release by 276.4% ± 0.8% and inhibited lipid accumulation by 47.8% ± 0.16%. Hispidin and DDK decreased intracellular triglyceride content by 79.5% ± 1.37% and 70.2% ± 1.4%, respectively, and all three compounds inhibited glycerol-3-phosphate dehydrogenase (GPDH) and pancreatic lipase, with hispidin and DDK being the most potent inhibitors. Finally, none of the three compounds reduced 3T3-L1 adipocyte viability. These results highlight the potential for developing hispidin and its derivatives as anti-obesity compounds.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Alpinia; Animals; Anti-Obesity Agents; Cell Survival; Cyclic AMP; Glycerol; Glycerolphosphate Dehydrogenase; Lipase; Lipids; Mice; Obesity; Plant Extracts; Pyrones; Triglycerides