Tropane alkaloids (TAs) are among the most valued chemical compounds known since pre-historic times. Poisonous plants from Solanaceae family (Hyoscyamus niger, Datura, Atropa belladonna, Scopolia lurida, Mandragora officinarum, Duboisia) and Erythroxylaceae (Erythroxylum coca) are rich sources of tropane alkaloids. These compounds possess the anticholinergic properties as they could block the neurotransmitter acetylcholine action in the central and peripheral nervous system by binding at either muscarinic and/or nicotinic receptors. Hence, they are of great clinical importance and are used as antiemetics, anesthetics, antispasmodics, bronchodilator and mydriatics. They also serve as the lead compounds to generate more effective drugs. Due to the important pharmacological action they are listed in the WHO list of essential medicines and are available in market with FDA approval. However, being anticholinergic in action, TA medication are under the suspicion of causing dementia and cognitive decline like other medications with anticholinergic action, interestingly which is incorrect. There are published reviews on chemistry, biosynthesis, pharmacology, safety concerns, biotechnological aspects of TAs but the detailed information on anticholinergic mechanism of action, clinical pharmacology, FDA approval and anticholinergic burden is lacking. Hence the present review tries to fill this lacuna by critically summarizing and discussing the above mentioned aspects.Graphical Abstract

Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae) led to the isolation of a new cucurbitane-type triterpenoid, aquilarolide A (1), along with five known compounds (2–6). The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR) experiments and mass spectrometry (MS) data and theoretical calculations of its electronic circular dichroism (ECD) spectra. Aquilarolide A, cucurbitacin E (3), cucurbitacin B (4), and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one (6) showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1, human lung squamous cell carcinoma NCI-H520, human lung adenocarcinoma A549, and paclitaxel-resistant A549 (A549/Taxol) cell lines. All four active compounds, with IC50 values ranging from 0.002 to 0.91 μM, had better inhibitory activities against A549/Taxol cells than paclitaxel (IC50 = 1.80 μM). Among them, cucurbitacin E (IC50 = 0.002 μM) is the most active. Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms.Graphical Abstract

Soil-derived fungi represent an insufficiently tapped reservoir for discovering new and bioactive natural products (NPs), and despite an ever-increasing number of unknown NPs have been discovered over the past few decades, much of the hidden biosynthetic potential is still in an urgent need to be disclosed. In this research, a chemical investigation was performed on a wetland soil-derived fungus Aspergillus calidoustus TJ403-EL05, leading to the isolation of a total of fourteen drimane sesquiterpenoids (1–14), incorporating three new ones, namely ustusols F–H (1–3). Their structures, comprising absolute configurations, were completely authenticated by widespread spectroscopic data, quantum chemical 13C NMR and ECD calculations, and X-ray crystallography experiments. Compound 14 exhibited moderate anti-inflammatory activity by inhibiting the LPS-induced NO release (IC50 = 25.6 μM).Graphical Abstract

Four new 14(13 → 12)-abeolanostane triterpenoids featuring extended π-conjugated systems, kadcoccitanes E–H (1–4), were obtained from the stems of Kadsura coccinea through using a HPLC − UV-guided approach. Their structural and configurational determination was accomplished through extensive spectroscopic analysis coupled with quantum chemical calculations. Kadcoccitanes E–H were tested for their cytotoxic activities against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, SW-480) but none of them exhibited activities at the concentration 40 μM.Graphical Abstract

Alstonia scholaris (L.) R. Br (Apocynaceae) is a well-documented medicinal plant for treating respiratory diseases, liver diseases and diabetes traditionally. The current study aimed to investigate the effects of TA on non-alcoholic fatty liver disease (NAFLD). A NAFLD model was established using mice fed a high-fat diet (HFD) and administered with TA (7.5, 15 and 30 mg/kg) orally for 6 weeks. The biochemical parameters, expressions of lipid metabolism-related genes or proteins were analyzed. Furthermore, histopathological examinations were evaluated with Hematoxylin–Eosin and MASSON staining. TA treatment significantly decreased the bodyweight of HFD mice. The concentrations of low-density lipoprotein (LDL), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also decreased significantly in TA-treated mice group, accompanied by an increase in high-density lipoprotein (HDL). Furthermore, TA alleviated hepatic steatosis injury and lipid droplet accumulation of liver tissues. The liver mRNA levels involved in hepatic lipid synthesis such as sterol regulatory element-binding protein 1C (SREBP-1C), regulators of liver X receptor α (LXRα), peroxisome proliferator activated receptor (PPAR)γ, acetyl-CoA carboxylase (ACC1) and stearyl coenzyme A dehydrogenase-1 (SCD1), were markedly decreased, while the expressions involved in the regulation of fatty acid oxidation, PPARα, carnitine palmitoyl transterase 1 (CPT1A), and acyl coenzyme A oxidase 1 (ACOX1) were increased in TA-treated mice. TA might attenuate NAFLD by regulating hepatic lipogenesis and fatty acid oxidation.

Mulberry Diels–Alder-type adducts (MDAAs) are unique phenolic natural products biosynthetically derived from the intermolecular [4 + 2]-cycloaddition of dienophiles (mainly chalcones) and dehydroprenylphenol dienes, which are exclusively distributed in moraceous plants. A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980. Structurally, the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups (Types A − H), while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs (Type I). These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures, remarkable biological activities, and synthetic challenges. The present review provides a comprehensive summary of the structural properties, bioactivities, and syntheses of MDAAs. Cited references were collected between 1980 and 2021 from the SciFinder, Web of Science, and China National Knowledge Internet (CNKI).Graphical Abstract

A new seco-anthraquinone, crispuside A (1), and three new 3,4-dihydronaphthalen-1(2H)-ones, napthalenones A-C (2–4), were isolated from the roots of Rumex crispus L., along with 10 known anthraquinones (6–14) and naphthalenone (5). Their structures were fully determined by extensive spectroscopic analyses, including ECD, and X-ray crystallography in case of compound 5, whose absolute configuration was determined for the first time. The isolates 1, 6–14 were evaluated for their anti-inflammatory and anti-fungal activity against three skin fungi, e.g., Epidermophyton floccosum, Trichophyton rubrum, and Microsporum gypseum. Most of the isolates showed weak anti-fungal and anti-inflammatory activity. Only compound 9 exhibited obvious anti-fungal activity against E. floccosum (MIC50 = 2.467 ± 0.03 μM) and M. gypseum (MIC50 = 4.673 ± 0.077 μM), while the MIC50 values of the positive control terbinafine were 1.287 ± 0.012 and 0.077 ± 0.00258 μM, respectively. The results indicated that simple emodin type anthraquinone is more potential against skin fungi than its oxyglucosyl, C-glucosyl and glycosylated seco analogues.Graphical Abstract

The global cosmetics market reached US$500 billion in 2017 and is expected to exceed US$800 billion by 2023, at around a 7% annual growth rate. The cosmetics industry is emerging as one of the fastest-growing industries of the past decade. Data shows that the Chinese cosmetics market was US$60 billion in 2021. It is expected to be the world's number one consumer cosmetics market by 2050, with a size of approximately US$450 billion. The influence of social media and the internet has raised awareness of the risks associated with the usage of many chemicals in cosmetics and the health benefits of natural products derived from plants and other natural resources. As a result, the cosmetic industry is now paying more attention to natural products. The present review focus on the possible applications of natural products from various biological sources in skin care cosmetics, including topical care products, fragrances, moisturizers, UV protective, and anti-wrinkle products. In addition, the mechanisms of targets for evaluation of active ingredients in cosmetics and the possible benefits of these bioactive compounds in rejuvenation and health, and their potential role in cosmetics are also discussed.

We examined the chemical constitution of the red alga Laurencia saitoi Perestenko, collected from Katsuura, Boso Peninsula, Chiba Prefecture, Japan. This specimen produced a new polyhalogenated acetogenin, named katsuurallene (1), which structure was determined by the spectral methods, along with known diterpene, deoxyparguerol (2) and triterpene, thyrsiferol (3). In this paper we describe the structural elucidation of katsuurallene together with some biological activities.

Antarctic krill oil is functional oil and has a complex phospholipids composition that poses difficulties in elucidating its effect mechanism on ulcerative colitis (UC). The mechanism of UC action was studied by bioinformatics, and the therapeutic effect of Antarctic krill phospholipids (APL) on dextran sulfate sodium (DSS)-induced colitis mice was verified. GO functional enrichment analysis uncovered an enrichment of these genes in the regulation of cell–cell adhesion, membrane region, signaling receptor activator activity, and cytokine activity. Meanwhile, the KEGG results revealed the genes were enriched in the TNF signaling pathway, pathogenic Escherichia coli infection, inflammatory bowel disease and tight junction. Animal experiments showed that APL treatment alleviated the UC symptoms and reduced inflammatory damage. Meanwhile, the expressions of the tight junction (TJ) proteins, ZO-1 and occludin, were restored, and the levels of IL-6 and TNF-α were reduced. Moreover, Firmicutes/Bacteroidetes ratio in the intestinal microbiota was regulated, and the contents of short-chain fatty acids metabolites were raised. These findings would provide an insight for the beneficial effects of APL and dietary therapy strategies for UC.

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is an orange-red, lipophilic keto-carotenoid pigment. It is majorly found in marine ecosystems particularly in aquatic animals such as salmon, shrimp, trout, krill, crayfish, and so on. It is also synthesized in microalgae Heamatococcus pluvialis, Chlorococcum, Chlorella zofingiensis, red yeast Phaffia rhodozyma and bacterium Paracoccus carotinifaciens. Some aquatic and terrestrial creatures regarded as a primary and secondary sources of the astaxanthin producing and accumulating it through their metabolic pathways. Astaxanthin is the powerful antioxidant, nutritional supplement as well as promising therapeutic compound, observed to have activities against different ravaging diseases and disorders. Researchers have reported remarkable bioactivities of astaxanthin against major non-communicable chronic diseases such as cardiovascular diseases, cancer, diabetes, neurodegenerative, and immune disorders. The current review discusses some structural aspects of astaxanthin. It further elaborates its multiple potencies such as antioxidant, anti-inflammatory, anti-proliferative, anti-cancer, anti-obese, anti-diabetic, anti-ageing, anti-TB, anti-viral, anti-COVID 19, neuro-protective, nephro-protective, and fertility-enhancing properties. These potencies make it a more precious entity in the preventions as well as treatments of prevalent systematic diseases and/or disorders. Also, the review is acknowledging and documenting its powerful bioactivities in relation with the pharmaceutical as well as nutraceutical applicability.Graphical Abstract

AbstractChemical investigation on the medicinal fungus Ganoderma australe led to the identification of ten new nor-lanostane triterpenes, namely two hexa-nor ones, ganoaustratetraenones A (1) and B (2), five penta-nor ones, ganoaustraldehydes A–E (3–7), and three tetra-nor ones ganoaustrenoic acids A–C (8–10). The chemical structures along with the absolute configurations were determined by extensive spectroscopic analysis of 1D & 2D NMR and HRESIMS data. The postulated biosynthesis pathways of these compounds were proposed. Ganoaustraldehydes A (3) and B (4) showed moderate inhibition against nitric oxide production in RAW264.7 macrophage cells with the respective IC50 values of 32.5, 34.2 µM (the IC50 of positive control pyrrolidine dithiocarbamate was 20.0 µM).Graphical Abstract

Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

Neptunia amplexicaulis is an herbaceous legume endemic to the Richmond area in central Queensland, Australia and is one of the strongest known Selenium hyperaccumulators on earth, showing significant potential to be utilised in Se phytoextraction applications. Here a protocol was established for in vitro micropropagation of Se hyperaccumulator N. amplexicaulis using nodal segments from in vitro-germinated seedlings. Shoot multiplication was achieved on Murashige and Skoog (MS) basal media supplemented with various concentrations of 6-Benzylaminopurine (BA) (1.0, 2.0, 3.0 mg L−1) alone or in combination with low levels of Naphthaleneacetic acid (NAA) (0.1, 0.2, 0.3 mg L−1), with 2.0 mg L−1 BA + 0.2 mg L−1 NAA found to be most effective. Elongated shoots were rooted in vitro using NAA, with highest root induction rate of 30% observed at 0.2 mg L−1 NAA. About 95% of the in vitro rooted shoots survived acclimatization. Clonally propagated plantlets were dosed with selenate/selenite solution and assessed for Se tissue concentrations using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) and found to retain their ability to hyperaccumulate. The protocol developed for this study has potential to be optimised for generating clonal plants of N. amplexicaulis for use in research and phytoextraction industry applications.

Bone marrow mesenchymal stem cells (BMSCs) are non-hematopoietic multipotent stem cells capable of differentiating into mature cells. Isoquercetin, an extract from natural sources, has shown promise as a potential treatment for osteoporosis. To investigate the therapeutic effects of isoquercetin on osteoporosis, bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro, and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days. We evaluated cell viability, osteogenic and adipogenic differentiation, as well as mRNA expression levels of Runx2, Alpl, and OCN in osteoblasts, and mRNA expression levels of Pparγ, Fabp4, and Cebpα in adipocytes. The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation, as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2, Alpl, and OCN in osteoblasts (P < 0.05). In contrast, isoquercetin inhibited adipogenic differentiation and decreased the mRNA expression levels of Pparγ, Fabp4, and Cebpα in adipocytes (P < 0.05). In vivo, isoquercetin treatment increased bone quantity and density in an osteoporosis model mice group, as determined by μCT scanning and immunohistochemistry (P < 0.05). These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.Graphical Abstract

A pair of new tetrahydrofuran lignan enantiomers, (±)-schibiculatin A [(±)-1], a new enedione lignan, schibiculatin B (2), two new cadinane-type sesquiterpenoids, schibiculatins C (3) and D (4), along with two known seco-cadinane-type sesquiterpenoids (5 and 6) and seven known miscellaneous lignans (7–13) were isolated from the stems of Schisandra bicolor var. tuberculate. The structures of 1–4 were elucidated by comprehensive analysis of their spectroscopic data, quantum chemical calculations, as well as single-crystal X-ray diffraction. A few isolated compounds were tested for their protective activities against corticosterone-induced apoptosis in PC12 cells. Among them, compounds 5 and 6 showed moderate activities.Graphical Abstract

Two novel compounds including a cyclohelminthol type polyketide (namely oxaleimide K, 1) and a maleimide derivative (namely peniroquefortine A, 2), and a new natural product (namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide, 3), together with four known compounds (4–7), were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment. Compound 1 represents the second example of a cyclohelminthol type polyketide, which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin (oct-1-en-3-yl) moiety, and compound 2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds. Remarkably, the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound 1 is determined by the single-crystal diffraction analysis for the first time, highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydrofuran moiety for 1 rather than a Z-configuration as previously reported in the biosynthesis study, which gives a new insight into the structural elucidation of this category of polyketides. Additionally, compound 1 exhibited significant cytotoxic activity against multiple tumor cells, especially against the Farage and SU-DHL-2 cells (IC50 < 20 µM, 48 h). Further mechanism study revealed that compound 1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.Graphical Abstract

From aerial parts of Austroeupatorium inulifolium was isolated the ent-nor-furano triol labdane austroeupatol 1. The compound 1 was treated with IBX showing an unexpected selectivity at the potentially oxidizable sites of the substrate yielding the 2-oxoaustroeupatol (2) and 2,19-dioxoaustroeupatol (3). The treatment of 2 with sodium periodate yields a heterocyclic derivative (ε-caprolactone derivate 4) formed by oxidative cleavage and unexpected intramolecular attack of the hydroxymethylene (C-19) oxygen to the ketonic carbon (C-2). A plausible mechanistic pathway for the obtention of compound 4 is proposed.Graphical Abstract

Indole diterpenoids (IDTs) are an essential class of structurally diverse fungal secondary metabolites, that generally appear to be restricted to a limited number of fungi, such as Penicillium, Aspergillus, Claviceps, and Epichloe species, etc. These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphosphate (GGPP) and an indole ring moiety derived from indole-3-glycerol phosphate (IGP). 3-geranylgeranylindole (3-GGI) is the common precursor of all IDTs. On this basis, it is modified by cyclization, oxidation, and prenylation to generate a large class of compounds with complex structures. These compounds exhibit antibacterial, anti-insect, and ion channel inhibitory activities. We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years, these compounds were reclassified, and their biological activities were summarized. This review will help to understand the structural diversity of IDTs and provide help for their physiological activities.Graphical Abstract

Three hitherto undescribed Stemona alkaloids, named stemajapines A–C (1–3), along with six known alkaloids (4–9), were isolated and identified from the roots of Stemona japonica (Blume) Miq. (Stemonaceae). Their structures were established by the analysis of the mass data, NMR spectra, and computational chemistry. Stemjapines A and B were degraded maistemonines without spiro-lactone ring and skeletal methyl from maistemonine. Concurrence of alkaloids 1 and 2 revealed an undescribed way to form diverse Stemona alkaloids. Bioassay results disclosed the anti-inflammatory natural constituents stemjapines A and C with IC50 values of 19.7 and 13.8 µM, respectively, compared to positive control dexamethasone with 11.7 µM. The findings may point out a new direction of Stemona alkaloids inaddition to its traditional antitussive and insecticide activities.