Correction: Yang et al. Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71. Int. J. Mol. Sci. 2013, 14, 9618

The authors wish to make the following corrections to this paper [...]

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.

REVIEW ON ANTIMICROBIAL AND ANTI ACNE POTENTIAL OF KAEMPFERIA SPP.

Acne is a general but somber skin disease, which affects approximately 80% adolescents and young adults in 11–30 age groups. 42.5 % of men and 50.9 % of women keep onto suffer from this disease into their twenties. Bacterial resistance is now at the alarming stage due to the irrational use of antibiotics. Hence, search for new lead molecule/bioactive and rational delivery of the existing drug (for better therapeutic effect) to the site of action is the need of the hour. Plants and plant-derived products have been an integral part of health care system since time immemorial. Therefore, plants that are currently used for the treatment of acne and those with a high potential are summarized in the present review. Most active plant extracts, namely, P. granatum, M. alba, A. anomala, and M. aquifolium exhibit minimum inhibitory concentration (MIC) in the range of 4–50 µg/mL against P. acnes, while aromatic oils of C. obovoides, C. natsudaidai, C. japonica, and C. nardus possess MICs 0.005–0.6 ?L/mL and phytomolecules such as rhodomyrtone, pulsaquinone, hydropulsaquinone, honokiol, magnolol, xanthohumollupulones, chebulagic acid and rhinacanthin-C show MIC in the range of 0.5–12.5 ?g/mL. Novel drug delivery tant plant leads in the treatment of acne have also been discussed.

Phytochemical Analysis Using UPLC-MSn Combined with Network Pharmacology Approaches to Explore the Biomarkers for the Quality Control of the Anticancer Tannin Fraction of Phyllanthus emblica L. Habitat in Nepal

Phyllanthus emblica L. is widely used in traditional Tibetan medicine for its therapeutic effects on treating liver, kidney, and bladder problems. We have reported that the tannin fraction has a good anti-hepatocellular carcinoma effect, but its active ingredients are not clear. This study was to find the active ingredients of the tannin fraction using UPLC-MSn and network pharmacology. First of all, the UPLC-MSn method was employed to obtain high-resolution mass spectra of different components, and 110 compounds were obtained. Then a network pharmacology method was used to find biomarkers for quality control. Network pharmacology results showed that gallic acid, punicalagin A, punicalagin B, methyl gallate, geraniin, corilagin, chebulinic acid, chebulagic acid, and ellagic acid should be the biomarkers of the tannin fraction. Furthermore, 9 components were detected in the serum, which also proved that they could be biomarkers, because we generally believe that the ingredients which are absorbed into the blood are effective. In the end, a simple method for simultaneously determining the contents of the 9 compounds was constructed by HPLC-DAD. This research established a new method to find biomarkers of traditional Chinese medicine. This is of great significance to improving the quality standards of Tibetan medicine.

Pentagalloylglucose, a phytochemical from Terminalia chebula can efficiently prevent SARS-CoV-2 entry: In Silico study

COVID-19 is the current health challenge across the world. It originated in Wuhan, China, and has now spread to more than 180 countries. It is a zoonotic disease which spreads through droplets. The severity of disease is likely to end with the discovery of vaccines only. Researchers are repurposing drugs to fill the gap between COVID-19 and vaccine designing. Broad-spectrum antiviral drugs are preferred but they exhibit side effects. We have screened pentagalloylglucose present in Terminalia chebula which can prevent SARS-CoV-2 entry to the host cell. In this study, we have taken 8 active phytochemicals of Terminalia chebula which include gallic acid, chebulic acid, chebulanin, neochebulinic acid, ellagic acid, chebulagic acid, chebulinic acid, and pentagalloyglucose against spike proteins (S1 and S2), Replicase Polyprotein, 3C-like protease (3CL pro), Papain-like protease (PLpro), RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. HADDOCK online server, Discovery Studio Visualizer and PyRx Vina tools were used to screen the potential component from T. chebula. It was analysed that pentagalloylglucose can be a better phytochemical against spike protein S1 similar to hemagglutinin of influenza virus. This phytochemical can be further used as a drug against SARS-CoV-2.

Virtual Screening Identifies Chebulagic Acid as an Inhibitor of the M2(S31N) Viral Ion Channel and Influenza A Virus

The increasing prevalence of drug-resistant influenza viruses emphasizes the need for new antiviral countermeasures. The M2 protein of influenza A is a proton-gated, proton-selective ion channel, which is essential for influenza replication and an established antiviral target. However, all currently circulating influenza A virus strains are now resistant to licensed M2-targeting adamantane drugs, primarily due to the widespread prevalence of an M2 variant encoding a serine to asparagine 31 mutation (S31N). To identify new chemical leads that may target M2(S31N), we performed a virtual screen of molecules from two natural product libraries and identified chebulagic acid as a candidate M2(S31N) inhibitor and influenza antiviral. Chebulagic acid selectively restores growth of M2(S31N)-expressing yeast. Molecular modeling also suggests that chebulagic acid hydrolysis fragments preferentially interact with the highly-conserved histidine residue within the pore of M2(S31N) but not adamantane-sensitive M2(S31). In contrast, chebulagic acid inhibits in vitro influenza A replication regardless of M2 sequence, suggesting that it also acts on other influenza targets. Taken together, results implicate chebulagic acid and/or its hydrolysis fragments as new chemical leads for M2(S31N) and influenza-directed antiviral development.