Isolation of naturally occurring novel isoflavonoids: an update

Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4',6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo. Co-treatment with TMF and glycitin synergistically promotes the proliferation and migration of both keratinocytes and dermal fibroblasts, with a 1:1 ratio of these compounds showing the greatest efficacy in our co-culture system. This keratinocyte-fibroblast interaction occurred via the secretion of TGF-β, and the induction of differentiation and proliferation was confirmed in both indirect and direct co-culture assays. In an excisional and burn wound animal model, mice treated with a 1:1 ratio of TMF and glycitin showed faster wound closure, regeneration and scar reduction than even the positive control drug. These data indicate that two isoflavones, TMF and glycitin, act synergistically to promote wound healing and anti-scarring and could potentially be developed together as a bioactive therapeutic for wound treatment.

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TMF and glycitin act synergistically on keratinocytes and fibroblasts to promote wound healing and anti-scarring activity

Amphimas pterocarpoides Harms (Leguminosae) is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP) in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females) for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent) and without biological relevance indicate a wide margin of safety for the traditional use of AP.

https://www.researchgate.net/profile/Job_Tchoumtchoua/publication/267047346_Safety_assessment_of_the_methanol_extract_of_the_stem_bark_of_Amphimas_pterocarpoides_Harms_Acute_and_subchronic_oral_toxicity_studies_in_Wistar_rats/links/5458bc960cf2bccc49125dac.pdf

Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats.

Background: To assess the potential phytoestrogenic effect of Amphimas pterocarpoides plant extract on the ovariectomy (OVX) induced bone loss in rats. Methods: Thirty nine female (10 month old) Wistar rats were separated into Controls (n=11), OVX (n=13) and OVX+AP groups (n=15). Measurements of Bone Mineral Density (BMD) were performed at baseline, 3 and 6 months after ovariectomy. After 6 months treatment, the rats were euthanized and femurs were extracted. The biomechanical properties were evaluated using the 3-point bending test. Results: The percentage changes of the mean values of the proximal tibia BMD from baseline to 3 months for Control, OVX and OVX+AP group were 6.25%, -21.82% and - 12.73% whereas at 6 months they were 8.108%, -32.134% and -22.410% respectively. The 3-point bending test revealed that the maximal load before fracture and the mean values for stress significantly increased in the treatment group compared with OVX rats. Body and uterine weights were similar between OVX and OVX+AP groups. Conclusion: This study is the first to demonstrate that orally administered Amphimas pterocarpoides extract for 6 months is effective in terms of improving bone quantity (Bone mineral density) and quality (biomechanical parameters), surrogate markers of reduced risk of fracture. Therefore, Amphimas pterocarpoides is a new class of phytoestrogen extract and it presents a remarkable antiosteoporotic activity. These properties make Amphimas pterocarpoides a promising herbal therapy for the prevention of postmenopausal osteoporosis induced by estrogen deficiency.

https://www.longdom.org/open-access/the-protective-effect-of-amphimas-pterocarpoides-plant-extract-on-bonemineral-density-and-strength-in-estrogen-deficient-ovariecto-2167-0412-1000269.pdf

The Protective Effect of Amphimas pterocarpoides Plant Extract on Bone Mineral Density and Strength in Estrogen Deficient Ovariectomized Wistar Rats

Isoformononetin, a dietary isoflavone protects against streptozotocin induced rat model of neuroinflammation through inhibition of NLRP3/ASC/IL-1 axis activation.

A new bis-isoflavone derivative, named amphiisoflavone (1), was isolated from the roots of Amphimas pterocarpoides, together with three known isoflavones, namely 8-methoxyisoformononetin (2), 6-methoxyisoformononetin (3) and isoformononetin (4). Chemical transformations carried out on compound 3 led to two new derivatives, 4´-acetoxy-6,7-dimethylisoflavone (3a) and 4´-O-prenyl- 6,7-dimethylisoflavone (3p), along with a known compound, 4´,6,7-trimethoxyisoflavone (3m). The structures of all compounds were elucidated from spectroscopic evidence, in particular by 1D and 2D NMR spectroscopic methods. These compounds were evaluated for their antioxidant properties and for their antimicrobial activities against a wide range of bacteria and fungi. Graphical Abstract Antimicrobial and Antioxidant Isoflavonoid Derivatives from the Roots of Amphimas pterocarpoides

Edwige P. Fodja Saah

Papers

Antimicrobial and Antioxidant Isoflavonoid Derivatives from the Roots of Amphimas pterocarpoides

Antimicrobial and Antioxidant Isoflavonoid Derivatives from the Roots of Amphimas pterocarpoides.

Antimycobacterial cycloartane derivatives from the roots of Trichilia welwistchii C. DC (Meliaceae)