A comprehensive review of herbacetin: From chemistry to pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbacetin is an active constituent of traditional Chinese medicines such as Ephedra sinica Stapf (MaHuang) and Sedum roseum (L.). Scop. (Hong JingTian). MaHuang was used to treat cough, asthma, fever, and edema for more than 5000 years, while Hong JingTian was used to treat depression, fatigue, cancers, and cardiovascular disease. Recent studies indicate that herbacetin and its glycosides play a critical role in the pharmacological activities of these herbs. However, currently, no comprehensive review on herbacetin has been published yet. AIM OF THE STUDY: This review aimed to summarize information on the chemistry, natural sources, and pharmacokinetic features of herbacetin, with an emphasis on its pharmacological activities and possible mechanisms of action. MATERIALS AND METHODS: A literature search was performed on the Web of Science, PubMed, and China Knowledge Resource Integrated databases (CNKI) using the search term "herbacetin" ("all fields") from 1935 to 2020. Information was also obtained from classic books of Chinese herbal medicine, Chinese pharmacopeia, and the database "The Plant List" (www.theplantlist.org). Studies have been analyzed and summarized in this review if they dealt with chemistry, taxonomy, pharmacokinetic, and pharmacological activity. RESULTS: Herbacetin is distributed in various plants and can be extracted or synthesized. It showed diverse pharmacological activities including antioxidant, antiviral, anti-inflammatory, anticancer, antidiabetic, and anticholinesterase. It is thought to have great potential in cancer treatment, especially colon and skin cancers. However, the bioavailability of herbacetin is low and the toxicity of herbacetin has not been studied. Thus, more studies are required to solve these problems. CONCLUSIONS: Herbacetin shows promising pharmacological activities against multiple diseases. Future research should focus on improving bioavailability, further studying its pharmacological mechanism, evaluating its toxicity and optimal dose, and performing the clinical assessment. We hope that the present review will serve as a guideline for future research on herbacetin.

New Acaciin-Loaded Self-Assembled Nanofibers as MPro Inhibitors Against BCV as a Surrogate Model for SARS-CoV-2.

BACKGROUND: SARS-COVID-2 has recently been one of the most life-threatening problems which urgently needs new therapeutic antiviral agents, especially those of herbal origin. PURPOSE: The study aimed to load acaciin (ACA) into the new self-assembled nanofibers (NFs) followed by investigating their possible antiviral effect against bovine coronavirus (BCV) as a surrogate model for SARS-COV-2. METHODS: ACA was identified using 1H-NMR and DEPT-Q 13C-NMR spectroscopy, the molecular docking study was performed using Autodock 4 and a modification of the traditional solvent injection method was applied for the synthesis of the biodegradable NFs. Different characterization techniques were used to inspect the formation of the NFs, which is followed by antiviral investigation against BCV as well as MTT assay using MDBK cells. RESULTS: Core/shell NFs, ranging between 80-330 nm with tiny thorn-like branches, were formed which attained an enhanced encapsulation efficiency (97.5 ± 0.53%, P<0.05) and a dual controlled release (a burst release of 65% at 1 h and a sustained release up to >24 h). The antiviral investigation of the formed NFs revealed a significant inhibition of 98.88 ± 0.16% (P<0.05) with IC50 of 12.6 µM against BCV cells. CONCLUSION: The results introduced a new, time/cost-saving strategy for the synthesis of biodegradable NFs without the need for electric current or hazardous cross-linking agents. Moreover, it provided an innovative avenue for the discovery of drugs of herbal origin for the fight against SARS-CoV-2 infection.

Tinocordiside from Tinospora cordifolia (Giloy) May Curb SARS-CoV-2 Contagion by Disrupting the Electrostatic Interactions between Host ACE2 and Viral S-Protein Receptor Binding Domain.

BACKGROUND: SARS-CoV-2 has been shown to bind the host cell ACE2 receptor through its spike protein receptor binding domain (RBD), required for its entry into the host cells. OBJECTIVE: We have screened phytocompounds from a medicinal herb, Tinospora cordifolia for their capacities to interrupt the viral RBD and host ACE2 interactions. METHODS: We employed molecular docking to screen phytocompounds in T. cordifolia against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy. RESULTS: 'Tinocordiside' docked very well at the center of the interface of ACE2-RBD complex, and was found to be well stabilized during MD simulation. Tinocordiside incorporation significantly decreased the electrostatic component of binding free energies of the ACE2-RBD complex (23.5 and 17.10 kcal/mol in the trajectories without or with the ligand, respectively). As the basal rate constant of protein association is in the order of 5 (105 to 106 M-1S-1), there might be no big conformational change or loop reorganization, but involves only local conformational change typically observed in the diffusion-controlled association. Taken together, the increase in global flexibility of the complex clearly indicates the start of unbinding process of the complex. CONCLUSION: It indicates that such an interruption of electrostatic interactions between the RBD and ACE2, and the increase in global flexibility of the complex would weaken or block SARSCoV- 2 entry and its subsequent infectivity. We postulate that natural phytochemicals like Tinocordiside could be viable options for controlling SARS-CoV-2 contagion and its entry into host cells.