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Integrating CADD and Herbal Informatics Approach to Explore Potential Drug Candidates Against HPV E6 Associated With Cervical Cancer
Published in Shazia Rashid, Ankur Saxena, Sabia Rashid, Latest Advances in Diagnosis and Treatment of Women-Associated Cancers, 2022
Arushi Verma, Jyoti Bala, Navkiran Kaur, Anupama Avasthi
As to the proposed two inhibitors of E6 oncoprotein, luteolin is in early Phase I clinical trials for other types of cancer including tongue carcinoma (NCT03288298), and daphnoretin recently patented as an effective treatment against tissue/organ rejection or GVHD [32]. Luteolin is reported to inhibit cell proliferation, survival signalling, angiogenesis and metastasis by inhibiting P13K-Akt, and it acts on apoptosis by activating DR5 and inhibiting Bcl-XL in various types of cancers [33]. Daphnoretin is known to exert its anticancer effects through the inhibition of cancer cell proliferation, the induction of G2/M-phase arrest and apoptosis [28]. Synergistic approaches by combining two or more of such herbal-based compounds are also in progress; for example, luteolin with quercetin and rutin are currently being tested for autism spectrum disorder (Phase II) (NCT01847521). Herein we are proposing the use of luteolin and daphnorectin as key inhibitors of HPV E6, and further validation of these in terms of in vitro and preclinical studies are required.
Medicinal Plants of Mongolia
Published in Raymond Cooper, Jeffrey John Deakin, Natural Products of Silk Road Plants, 2020
Narantuya Samdan, Odonchimeg Batsukh
Chemical constituents of S. chamaejasme roots are as follows: 73.5% holocellulose, 39.7% α-cellulose, and 17.6% lignin. It is noted that the holocellulose content is comparable to that of various non-woody plants indicating that S. chamaejasme root is a potential raw material for lignocellulosic paper production (Li et al., 2014). Roots contain sugars, organic acids, saponins, 1.2% tannins; 0.35% flavonoids: 5,7-dihydroxy-4′, 11-dimethoxy-3′, 14-dimethylbenzoflavanone (Liu et al., 1995), ruixianglangdusu A and B, 4′, 4′″, 5,5″, 7,7″-hexahydroxy-3,3″-biflavone (Xu et al., 2001a), 7-methoxyneochamaejasmin A (Feng et al., 2002); 0.3% coumarins: sfondine, isobergapten, pimpinellin, isopimpinellin, umbelliferone, daphnoretin, bicoumastechamin (Xu et al., 2001b), diterpenes (Jiang et al., 2002); lignans: (+)-kusunokinin, lirioresinol-B, magnolenin C, (−)-pinoresinol monomethyl ether, (−)-pinoresinol, (+)-matairesinol, isohinokinin, and (−)-eudesmin (Xu et al., 2001b); steroids: daucosterol, β-sitosterol (Liu et al., 1995). The herb contains coumarins: daphnorin, daphnetin, daphnoretin (Figure 1.27), and daphnetin 8-O-β-D-glycopyranoside, chamaejasmoside (Narantuya, 1996; Narantuya et al., 2000).
Discovery of caffeoylisocitric acid as a Keap1-dependent Nrf2 activator and its effects in mesangial cells under high glucose
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Huankai Yao, Wenting Zhang, Feng Yang, Fengwei Ai, Dan Du, Yan Li
In the discovery of Nrf2 activators, natural products have become the pool of candidates. Some natural compounds such as curcumin, resveratrol, sulforaphane, and cinnamaldehyde showed significant activity to activate Nrf224. Especially bardoxolone methyl (CDDO-ME), a synthetic derivative of oleananic acid, as an Nrf2 activator has been in phase 3 trial involving patients with DN. However, the trial was terminated due to the strong adverse effects related to safety25. In searching for Nrf2 activators 3-phenylpropanoic acid is an important fragment26, the moieties derived from which can also be found in many natural compounds (Figure 1). Our previous investigations have revealed polypodiside and daphnoretin-7-O-β-D-glucopyranoside as Nrf2 activators attenuated oxidative stress and accumulation of ECM mesangial cells under high glucose27,28, and both of them possess cinnamoyl group which is analogue of 3-phenylpropanoic acid. However, these compounds are dimers with glucose moiety, which results in the complex structures. To find novel Nrf2 activators, we have screened the natural compounds with cinnamoyl moiety in our group and caffeoylisocitric acid has been raised. As a rare cinnamic acid derivative, caffeoylisocitric acid is a condensed ester of a caffeoylic acid and an isocitric acid, which is first found in Amaranthus cruentus29. Recently, we have identified it from Potentilla fragarioides L30, whereas there is no report about its biological activity. Herein we report its effects on Nrf2 activation and certain activities associated with DN using cell-based assays.
In vitro evaluation of intestinal absorption of tiliroside from Edgeworthia gardneri (Wall.) Meisn.
Published in Xenobiotica, 2021
Xiongwei Yin, Min Wang, Zhining Xia
The intestinal absorption data of WAE obtained by in vivo animal oral administration models and three in vitro intestinal absorption models were compared and summarised (Figure 2 and Table 2). In the oral administration model, 11 chemical components, including helichrysoside (1), gardnerol B (2), edgeworoside C (3), kaempferol-3-O-β-rutinoside (4), daphnoretin 5-O-β-glucopyranosyl-(1→2)-β-D-glucopyranoside (5), astragalin (6), edgeworic acid (8), edgeworoside A (9), trans-tiliroside (10), cis-tiliroside (11), and daphnoretin (12), were detected by HPLC-MS/MS in rat plasma. The absorption of ten chemical components was detected in the everted gut sac model. In the everted gut sac model, two components, including bioactive trans-tiliroside (10) and cis-tiliroside (11), were not detected, but 8-(3(2,4-benzenediol)-propionic acid methyl ester)-coumarin-7-β-D-glucoside (7) was detected. In the Caco-2 cell model, ten chemical components of WAE were detected. It is worth mentioning that the absorption of peaks of trans-tiliroside (10), and cis-tiliroside (11) were observed. Two components, including daphnoretin 5-O-β-glucopyranosyl-(1→2)-β-D-glucopyranoside (5) and edgeworoside A (9), were not detected. However, 8-(3(2,4-benzenediol)-propionic acid methyl ester)-coumarin-7-β-D-glucoside (7), which was detected in the everted gut sac model, was also detected in the Caco-2 cell model. Importantly, the result of Ussing chamber model was similar to that of the oral administration model. Eleven chemical components were detected by both models and only one component (8-(3(2,4-benzenediol)-propionic acid methyl ester)-coumarin-7-β-D-glucoside) (7) presented different absorption results among different models. As mentioned before, 8-(3(2,4-benzenediol)-propionic acid methyl ester)-coumarin-7-β-D-glucoside (7) was detected in three absorption models in vitro. However, 8-(3(2,4-benzenediol)-propionic acid methyl ester)-coumarin-7-β-D-glucoside (7) has not been found in vivo model. The result might be caused by its rapid metabolism.