Chrysosplenetin B – an O-methylated flavonol

Chrysosplenetin B is a tetramethoxyflavone that is the 3,6,7,3'-tetramethyl ether derivative of quercetagetin. It has a role as an antiviral agent and a plant metabolite. It is a tetramethoxyflavone and a dihydroxyflavone. It derives from a quercetagetin [1].

Chrysosplenetin B is an O-methylated flavonol. It can be found in the root of Berneuxia thibetica and in Chamomilla recutita [2].

Artemisinin (ART) is an efficacious and safe anti-malarial drug but has low oral bioavailability and auto-induction profiles during multiple dosing. The pharmacokinetic disadvantages have been found to partially depend on the induction of cytochrome P-450 enzymes by ART and resulted in the therapeutic failure due to insufficient drug levels. The present study, therefore, investigated the impacts of chrysosplenetin B (CHR), a polymethoxylated flavonoid from Artemisia annua, on the pharmacokinetics and the anti-malarial efficacy of ART against Plasmodium berghei. The inhibition of CHR on enzymatic activity of CYP1A2, CYP2A, CYP2C19, CYP2D6, CYP2E1, and CYP3A in rat liver microsome was also investigated. IC50, Km, Ki, and inhibitory type of CHR were respectively calculated [3].

Chrysosplenetin B is an O-methylated flavonol compound isolated from the plant Chamomilla recutita and Laggera pterodonta. The aim of Guoju Hong’s research is to evaluate the function of Chrysosplenetin on osteogenesis of human-derived bone marrow stromal cells (hBMSCs) and inhibition of estrogen deficiency-induced osteoporosis via the Wnt/β-catenin signaling pathway. hBMSCs are cultured and treated by Chrysosplenetin B in the absence or presence of Wnt inhibitor dickkopf-related protein 1 (DKK1) or bone morphogenetic protein 2 (BMP2) antagonist Noggin. RT-qPCR is taken to identify the genetic expression of target genes of Wnt/β-catenin pathway and osteoblast-specific markers. The situation of β-catenin is measured by western blot and immunofluorescence staining. An ovariectomized (OVX) mouse model is set up to detect the bone loss suppression by injecting Chrysosplenetin B. Micro-CT and histological assay are performed to evaluate the protection of bone matrix and osteoblast number. Serum markers related with osteogenesis are detected by ELISA. It is found that Chrysosplenetin Btime-dependently promoted proliferation and osteoblastogenesis of hBMSCs reaching its maximal effects at a concentration of 10 μM. The expressions of target genes of Wnt/β-catenin pathway and osteoblast-specific marker genes are enhanced by Chrysosplenetin Btreatment. Furthermore, the phosphorylation of β-catenin is decreased, and nuclear translocation of β-catenin is promoted by Chrysosplenetin B. Osteogenesis effects mentioned above are founded to be blocked by DKK1 or BMP2 antagonist Noggin. In vivo study reveals that Chrysosplenetin Bprevents estrogen deficiency-induced bone loss in OVX mice detected by Micro-CT, histological analysis, and ELISA. Their study demonstrates that Chrysosplenetin Bimproves osteoblastogenesis of hBMSCs and osteogenesis in estrogen deficiency-induced bone loss by regulating Wnt/β-catenin pathway [4].

References

[1] https://pubchem.ncbi.nlm.nih.gov/compound/Chrysosplenetin
[2] https://en.wikipedia.org/wiki/Chrysosplenetin
[3] Shijie Wei, Hongyan Ji, Bei Yang, Liping Ma, Zhuchun Bei, Xiang Li, Hongwan Dang, Xiaoying Yang, Cheng Liu, Xiuli Wu & Jing Chen, Impact of chrysosplenetin on the pharmacokinetics and anti-malarial efficacy of artemisinin against Plasmodium berghei as well as in vitro CYP450 enzymatic activities in rat liver microsome, Malaria Journal volume 14, Article number: 432 (2015).
[4] Guoju Hong, Xiaoming He, Yingshan Shen, Xiaojun Chen, Fang Yang, Peng Yang, Fengxiang Pang, Xiaorui Han, Wei He & Qiushi Wei, Chrysosplenetin promotes osteoblastogenesis of bone marrow stromal cells via Wnt/β-catenin pathway and enhances osteogenesis in estrogen deficiency-induced bone loss, Stem Cell Research & Therapy volume 10, Article number: 277 (2019)