Panaxindole, a novel indole alkaloid N-glucoside from the leaves of Panax vietnamensis Ha et Grushv. (Vietnamese ginseng).

Vietnamese ginseng (Panax vietnamensis Ha and Grushv., Araliaceae) is indigenous in the central highlands of Vietnam and the southernmost distribution in the Panax genus. Like other ginseng, Vietnamese ginseng is well known has been used as a tonic and for management of certain diseases in the traditional medicine. Nevertheless, it is noteworthy that in respect to the long history in use and systematic studied on Korean ginseng (P. ginseng), American ginseng (P. quinquefolius), Japanese ginseng (P. japonicus), and Chinese ginseng (P. notoginseng), the up-to-date published database on Vietnamese ginseng is relatively much less extensive. In our ongoing research on the promising Vietnamese medicinal plants, the present phytochemical investigation of the ethanol extract of the leaves of Panax vietnamensis led to the isolation of three compounds (1-3), including a new indole alkaloid N-glycoside (1) and two known compounds. Their structures were elucidated based on extensive physiochemical and chemical methods, especially the interpretation of NMR and MS spectra. The absolute configuration of 1 was determined based on the comparison of its experimental and theoretical ECD spectra along with NMR calculation. Compound 1 is naturally isolated N-glycoside, which is rarely found in natural products. The isolated compounds showed weak or no inhibitory activity against acetylcholinesterase enzyme (AChE).

Chemical constituents of Desmodium triflorum and their antifungal activity against various phytopathogenic fungi.

In the course of finding new antifungal natural compounds against plant pathogens, the methanol extract of Desmodium triflorum was investigated phytochemically. From n-butanol-soluble fraction, seven compounds (1-7) were isolated and structurally elucidated. Of which, six compounds belong to flavone 6- or 8-C-glycoside class (1-6). Three major compounds (1-3) exhibited moderate in vitro antifungal activity against Sclerotium rolfsii, Fusarium oxysporum f. sp. cubense, and Phytophthora palmivora. Compound 1 (IC50 = 162.1 µg/mL) was most active against S. rolfsii in a dose-dependent manner. At 300 µg/mL, compounds 1 and 2 significantly inhibited P. palmivora, whereas compound 3 lacked effectiveness. In addition, the nanoemulsion of the methanol extract with a droplet size of 12.2 nm displayed an excellent inhibition against S. rolfsii and P. palmivora compared with the normal extract. The presence of 1 (0.846%) and 2 (0.759%) in the methanol extract may attribute to the antifungal activity of D. triflorum. These results proved the potential of D. triflorum and its C-glycoside flavonoids against phytopathogenic fungi for the first time. Besides, an enhancement in the effectiveness of nanoemulsion containing D. triflorum extract against the fungi was confirmed. The structural characteristics of 1 and 2 could be considered to develop new fungicidal substances in the future.

Chemical constituents of Antidesma bunius aerial parts and the anti-AGEs activity of selected compounds.

Thirty-three natural products were isolated from the aerial parts of Antidesma bunius, Euphorbiaceae, a plant used in Vietnamese traditional medicine against rheumatoid arthritis. All compounds were reported the first time for this species, and nine constituents resembled undescribed natural products, noticeably three coumarinolignans with 2,2-dimethyl-1,3-dioxolane moiety, two cyclopeptides, and two furofuran-type lignans connected with a phenylpropanoid moiety. The individual structures were elucidated by combining NMR and MS data, and their configuration was established by NOESY and ECD experiments and NMR calculations. Compounds with sufficient amount were analyzed for their inhibition of advanced glycation endproducts (AGEs) formation, metabolites involved in many diseases like Alzheimer, joint diseases or diabetes. With IC50 values below 0.2 mM rutin and p-hydroxyphenethyl trans-ferulate showed to be moderately active, both still being 10-times more active than the positive control aminoguanidine.

Fissistigma genus - a review on phytochemistry and pharmacological activities.

The genus Fissistigma belongs to Annonaceae family and is mainly distributed in tropical areas of Asia. Many species from this genus have long been used for medicinal purposes in China and Vietnam. To date, there have been a number of studies on both phytochemical and pharmacological aspects of Fissistigma species, which indicated that the genus is a rich source of diverse and novel bioactive compounds, including alkaloids, terpenoids and phenolic derivatives. The review aims to summarise past study results as well as analyse future directions of Fissistigma species research.

Triterpenoids from the genus Gynostemma: Chemistry and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: G. pentaphyllum, also known as Jiao-Gu-Lan, has been used traditionally as folk remedies for many diseases, including diabetes mellitus, metabolic syndrome, aging, and neurodegenerative diseases in China and some countries in East and Southeast Asia. It is considered as an "immortality herb" in Guizhou Province, because it was consumed regularly by the elderly native inhabitants. Other species of the same genus Gynostemma such as G. longipes and G. laxum have been used as alternatives to G. pentaphyllum in ethno-medicine in Vietnam and other Asian countries. AIM OF THE REVIEW: The review aims to summarize up-to-date study results on Gynostemma species, including traditional usage, phytochemical profile, pharmacological activities, and toxicological studies, in order to suggest future research orientation and therapeutic applications on acute and chronic diseases. MATERIALS AND METHODS: The relevant literature on the genus Gynostemma was gathered from secondary databases (Web of Science and PubMed), books, and official websites. The latest literature cited in this review was published in February 2020. RESULTS: The genus Gynostemma has been widely used in traditional medicine, mainly for treatment of diabetes, hypertension, obesity, and hepatosteatosis. To date, 328 dammarane-type saponins were isolated and structurally elucidated from Gynostemma species. Crude extracts, saponin-rich fractions (gypenosides), and pure compounds were reported to show a wide range of pharmacological activities in both in vitro and in vivo experiments. The most notable pharmacological effects were anti-cancer, cardioprotective, hepatoprotective, neuroprotective, anti-diabetic, anti-obesity, and anti-inflammatory activities. Toxicological studies were conducted only on G. pentaphyllum, showing that the plant extracts were relatively safe in both acute and long-term toxicity experiments at the given dosage while no toxicological studies were reported for the other species. CONCLUSIONS: The review summarizes current studies on traditional uses, phytochemistry, biological properties, and toxicology of medicinal Gynostemma species. Till now, the majority of publications still focused only on G. pentaphyllum. However, the promising preliminary data of other Gynostemma species indicated the research potential of this genus, both in phytochemical and pharmacological aspects. Furthermore, clinical data are required to evaluate the efficacy and undesired effects of crude extracts, standard saponin fractions, and pure compounds prepared from Gynostemma medicinal plants.

Ethnopharmacology, Phytochemistry, and Pharmacology of Syzygium nervosum.

Syzygium nervosum, which belongs to the Myrtaceae plant family, is widely distributed and cultivated in South East Asian countries. The decoction of S. nervosum leaves and flower buds has been consumed regularly as a beverage among the Vietnamese and Chinese communities. In addition, it has also been used in traditional medicine for a variety of purposes, notably for influenza, skin diseases, and digestive conditions. To date, there has been a considerable number of publications on chemical profiling and pharmacological activities of S. nervosum crude extract and pure isolated compounds. Our analysis indicated the characteristic chemical scaffolds and potential bioactivities on cancer, diabetes, and inflammatory diseases of this plant. The review aims to summarize up-to-date past study results and suggest future research direction on this species, in order to promote clinical applications of S. nervosum.

Antiviral Activities of Compounds Isolated from Pinus densiflora (Pine Tree) against the Influenza A Virus.

Pinus densiflora was screened in an ongoing project to discover anti-influenza candidates from natural products. An extensive phytochemical investigation provided 26 compounds, including two new megastigmane glycosides (1 and 2), 21 diterpenoids (3-23), and three flavonoids (24-26). The chemical structures were elucidated by a series of chemical reactions, including modified Mosher's analysis and various spectroscopic measurements such as LC/MS and 1D- and 2D-NMR. The anti-influenza A activities of all isolates were screened by cytopathic effect (CPE) inhibition assays and neuraminidase (NA) inhibition assays. Ten candidates were selected, and detailed mechanistic studies were performed by various assays, such as Western blot, immunofluorescence, real-time PCR and flow cytometry. Compound 5 exerted its antiviral activity not by direct neutralizing virion surface proteins, such as HA, but by inhibiting the expression of viral mRNA. In contrast, compound 24 showed NA inhibitory activity in a noncompetitive manner with little effect on viral mRNA expression. Interestingly, both compounds 5 and 24 were shown to inhibit nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Taken together, these results provide not only the chemical profiling of P. densiflora but also anti-influenza A candidates.

Pharmacological Targets of Kaempferol Within Inflammatory Pathways-A Hint Towards the Central Role of Tryptophan Metabolism.

The flavonoid kaempferol is almost ubiquitously contained in edible and medicinal plants and exerts a broad range of interesting pharmacological activities. Interactions with central inflammatory processes can be exploited to treat or attenuate symptoms of disorders associated with chronic immune activation during infections, malignancies, and neurodegenerative or cardiovascular disorders. Many drugs, phytochemicals, and nutritional components target the catabolism of the essential amino acid tryptophan by indoleamine 2,3-dioxygenase 1 (IDO-1) for immunomodulation. We studied the effects of kaempferol by in vitro models with human peripheral blood mononuclear cells (PBMC) and THP-1 derived human myelomonocytic cell lines. Kaempferol suppressed interferon-γ dependent immunometabolic pathways: Formation of the oxidative stress biomarker neopterin and catabolism of tryptophan were inhibited dose-dependently in stimulated cells. In-silico docking studies revealed a potential interaction of kaempferol with the catalytic domain of IDO-1. Kaempferol stimulated nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-treated THP-1 cells, thereby increasing the mRNA expression of interleukin (IL) 1 beta, tumor necrosis factor, and nuclear factor kappa B subunit 1, while IL6 was downregulated. Data suggest that concerted effects of kaempferol on multiple immunologically relevant targets are responsible for its immunomodulatory activity. However, the immunosuppressive effects may be more relevant in a T-cell dominated context.

Terpenoids from the Stems of Fissistigma polyanthoides and Their Anti-Inflammatory Activity.

Twelve new terpenoids (1-12) were isolated from the stems of Fissistigma polyanthoides, an anti-inflammatory medicinal plant traditionally used in Vietnam. Most of them (1-9) possess a sesquiterpenoid backbone (e.g., guaiane, germacrane, and cadinane) connected to a 2'-O-trans-cinnamoyl)-ß-d-glucopyranose moiety, which is rare in Nature. Among them, compounds 4 (5/8-fused ring) and 6 (spiran [4,5] ring) represent uncommonly rearranged sesquiterpenoids. Compounds 10-12 are a novel monoterpene and two megastigmane derivatives, respectively. The individual structures were elucidated by combining NMR and MS data, and their configuration was established in NOESY and ECD experiments. Compounds 1-9 were also examined for their potential to interact with nuclear factor-kappa B activator protein 1 (NF-κB/AP-1) signaling by using the myelomonocytic reporter cell line THP-1Blue-CD14. Compounds 1-5 showed dose-dependent inhibitory effects [IC50 13.7 µM (1) to 49.0 µM (5)] on lipopolysaccharide-stimulated cells. However, compounds 1 to 4 also negatively affected cell viability in the same concentration range, while compound 5 was less potently cytotoxic.

Phytochemical and analytical characterization of constituents in Urceola rosea (Hook. & Arn.) D.J. Middleton leaves.

In Vietnam and China the leaves of Urceola rosea are widely used as herbal remedy and food. However, in contrast to the plants stem, little information was available on major constituents. In this study, the first in-depth phytochemical investigation of U. rosea leaves is described, which resulted in the isolation of thirteen compounds, mainly flavonoids (kaempferol and quercetin derivatives) and triterpenes. Furthermore, an analytical procedure for the quantification of five major compounds was developed. The HPLC separation was performed on a Synergi MAX-RP column using acetonitrile and 0.1% formic acid as mobile phase. Method validation confirmed that the assay shows good linearity (R2≥0.9997), precision (intra-day R.S.D≤4.31%, inter-day R.S.D≤3.52%) and accuracy (recovery rates ranged from 96.8 to 102.6%). Detection limits were always lower than 0.07µg/mL. The analysis of several plant samples revealed distinct differences, as for example the content of total phenolics varied from 0.44 to 1.73%.

Antiviral phenolics from the leaves of Cleistocalyx operculatus.

During the screening program for anti-influenza agents from medicinal plants, the ethanolic extract of Cleistocalyx operculatus leaves was found to exhibit potential neuraminidase (NA) inhibitory activity. Bioassay-directed fractionation led to the isolation of two new acetophenones (1 and 2) and one new flavanone (3), along with six known compounds (4-9). The structures of all isolated compounds were elucidated using various spectroscopic methods and through comparison with the previous literature. Compounds 6 and 8 exhibited strong enzymatic inhibition on various neuraminidases from different influenza viruses, including H1N1, H9N2, novel H1N1, and oseltamivir-resistant novel H1N1 (H274Y mutation) expressed in HEK293 cells (IC50 values ranging from 5.07 ± 0.94 µM to 9.34 ± 2.52 µM, respectively). Kinetic experiments revealed the non-competitive inhibitory mode of both compounds 6 and 8. Furthermore, these flavonoids reduced the cytopathic effect of the H1N1 virus in MDCK cells. The present study suggests the potential of two flavonoids (6 and 8) as new lead compounds for the development of novel NA inhibitors in the future.

Oleanane triterpenes from the flowers of Camellia japonica inhibit porcine epidemic diarrhea virus (PEDV) replication.

Porcine epidemic diarrhea virus (PEDV) infections have resulted in a severe economic loss in the swine industry in many countries due to no effective treatment approach. Fifteen oleanane triterpenes (1-15), including nine new ones (1-4 and 10-14), were isolated from the flowers of Camellia japonica, and their molecular structures were determined by extensive spectroscopic methods. These compounds were evaluated for their antiviral activity against PEDV replication, and the structure-activity relationships (SARs) were discussed. Compounds 6, 9, 11, and 13 showed most potent inhibitory effects on PEDV replication. They were found to inhibit PEDV genes encoding GP6 nucleocapsid, GP2 spike, and GP5 membrane protein synthesis based on RT-PCR data. Western blot analysis also demonstrated their inhibitory effects on PEDV GP6 nucleocapsid and GP2 spike protein synthesis during viral replication. The present study suggested the potential of compounds 6, 9, 11, and 13 as promising scaffolds for treating PEDV infection via inhibiting viral replication.

New rocaglamide derivatives from Vietnamese Aglaia species.

Phytochemical analysis of the leaves of different Aglaia species collected in Vietnam yielded eight rocaglamide derivatives, which are responsible for the strong insecticidal activity against Spodoptera littoralis, including rocaglamide A (1), rocaglamide 1 (2), rocaglamide W (3), rocaglamide AB (4), rocaglamide J (5), rocaglaol (6), rocaglamide S (7) and the new rocaglamide AY (8). The structures of these compounds were elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESI-MS) and HRESIMS data.