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Five new 2-(2-phenylethyl)chromone derivatives and three new sesquiterpenoids from the heartwood of Aquilaria sinensis, an aromatic medicine in China
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Lu Zhang, Ping Yi, Hui Yan, Xiao-Nian Li, Meng-Yuan Xia, Jun Yang, Ji-Feng Luo, Yue-Qiu He, Yue-Hu Wang
Natural Products and Bioprospecting. 2022, 12 (1): 1-14.
DOI: 10.1007/s13659-022-00326-3
Five new 2-(2-phenylethyl)chromone derivatives, (5S,6R,7R,8S,7'R)-7'-hydroxyagarotetrol (1), (5S,6R,7R,8S,7'S)-7'-hydroxyagarotetrol (2), (6S,7S,8R)-2-[2-(4-methoxyphenyl)ethyl]-6,7,8-trihydroxy-5,6,7,8-tetrahydrochromone (3), (6S,7S,8R)-2-(2-phenylethyl)-6,7,8-trihydroxy-5,6,7,8-tetrahydrochromone (4), (5S,6R,7S,8R)-2-(2-phenylethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydro-8-[2-(2-phenylethyl)-7-methoxychromonyl-6-oxy]chromone (5), three new sesquiterpenoids, (4S,5S,7S,8S,10S,13R)-7,8,13-trihydroxyrotunda-1,11-dien-3-one (6), (4S,5S,7S,8S,10S,13S)-7,8,13-trihydroxyrotunda-1,11-dien-3-one (7), and (4R,5S,7S,8S,10S,13S)-7,8,13-trihydroxyrotunda-1,11-dien-3-one (8), along with 14 known compounds were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). The chemical structures of these new compounds were elucidated by 1D and 2D NMR and MS data, single-crystal X-ray diffraction analysis, and electronic circular dichroism (ECD) calculations. The neuroprotective activities of these isolates were evaluated using an in vitro model of rat adrenal pheochromocytoma (PC12) cell injury induced by corticosterone. At concentrations from 5 to 40 μM, compounds 4 and 6, agarotetrol (9), and 6-hydroxy-2-(2-phenylethyl)chromone (17) showed significant protective activities against corticosterone-induced PC12 cell injury (P<0.001).
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Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2
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Wenting Liu, Weikang Zheng, Liping Cheng, Ming Li, Jie Huang, Shuzheng Bao, Qiang Xu, Zhaocheng Ma
Natural Products and Bioprospecting. 2022, 12 (1): 1-10.
DOI: 10.1007/s13659-022-00325-4
The most recent outbreak of 2019 novel coronavirus, named as COVID-19, caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020. Identification of effective antiviral agents to combat the novel coronavirus is urgently needed. Citrus fruit peel or wild citrus are rich in flavonoids, and clinically documented for roles in relief of cough and promotion of digestive health. Therefore, citrus fruits are assumed to possess antivirus activities or enhance the host immunity. A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro. We determined six flavonoid compounds' content in three citrus species by using LC-MS technique. The content of naringin and naringenin was at higher levels in pummelo. Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange. The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines (COX-2, iNOS, IL-1β and IL-6) induced by LPS in Raw macrophage cell line, and may restrain cytokine through inhibiting HMGB1 expression in a mouse model. The results revealed that naringin may have a potential application for preventing cytokine storm. We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2 (ACE 2), which is a receptor of the coronavirus. Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids, the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.
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Novel insights on acetylcholinesterase inhibition by Convolvulus pluricaulis, scopolamine and their combination in zebrafish
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Kalyani Bindu Karunakaran, Anand Thiyagaraj, Kirankumar Santhakumar
Natural Products and Bioprospecting. 2022, 12 (1): 1-15.
DOI: 10.1007/s13659-022-00332-5
Acetylcholinesterase (AChE) inhibitors increase the retention of acetylcholine (ACh) in synapses. Although they alleviate cognitive deficits in Alzheimer's disease, their limited benefits warrant investigations of plant extracts with similar properties. We studied the anti-AChE activity of Convolvulus pluricaulis (CP) in a zebrafish model of cognitive impairment induced by scopolamine (SCOP). CP is a perennial herb with anti-amnesiac and anxiolytic properties. It contains alkaloid, anthocyanin, coumarin, flavonoid, phytosterol and triterpenoid components. Isoxazole (ISOX) was used as a positive control for AChE inhibition. CP-treated 168 hpf larvae showed a similar pattern of AChE inhibition (in the myelencephalon and somites) as that of ISOX-treated larvae. CP was superior to ISOX as evidenced by the retention of avoidance response behavior in adult zebrafish. Molecular docking studies indicated that ISOX binds Ser203 of the catalytic triad on the human AChE. The active components of CP-scopoletin and kaempferol-were bound by His447 of the catalytic triad, the anionic subsite of the catalytic center, and the peripheral anionic site. This suggested the ability of CP to mediate both competitive and non-competitive modes of inhibition. Surprisingly, SCOP showed AChE inhibition in larvae, possibly mediated via the choline-binding sites. CP+SCOP induced a concentration-dependent increase in AChE inhibition and ACh depletion. Abnormal motor responses were observed with ISOX, CP, ISOX+SCOP, and CP+SCOP, indicative of undesirable effects on the peripheral cholinergic system. Our study proposes the examination of CP, SCOP, and CP+SCOP as potential AChE inhibitors for their ability to modulate cognitive deficits.
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Furanocembranoid from the Okinawan soft coral Sinularia sp.
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Misaki Nagasaka, Kazuki Tani, Keisuke Nishikawa, Riri Kinjo, Takahiro Ishii
Natural Products and Bioprospecting. 2022, 12 (1): 1-7.
DOI: 10.1007/s13659-022-00330-7
One new furanocembranoid diterpene, 11-hydroxy-Δ12(13)-pukalide (1), along with six known secondary metabolites, 11-acetoxy-Δ12(13)-pukalide (2), 13α-acetoxypukalide (3), pukalide (4), 3α-methoxyfuranocembranoid (5), Δ9(15)-africanene (6), and methyl (5'E)-5-(2',6'-dimethylocta-5',7'-dienyl)furan-3-carboxylate (7) were isolated from the Okinawan soft coral Sinularia sp. Their chemical structures were elucidated based on spectroscopic analysis (FTIR, NMR, and HRESIMS), and the relative stereochemistry of 1 was determined by NOESY experiments and acetylation, which yielded derivative 2. In addition, compounds 1 and 7 exhibited toxicity in the brine shrimp lethality test.
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