New alkylamides from the pericarps of Zanthoxylum schinifolium.

The pericarps of Zanthoxylum schinifolium Sieb. et Zucc were called "green huajiao", which were used as traditional folk medicine and popular seasoning in China. In this study, twenty-seven alkylamides, including a rare alkylamide containing two amide groups (1), an alkylamide with a furan ring (5), six new alkylamide analogues (2-4, 6-8), together with nineteen known alkylamides (9-27) were isolated from green huajiao. Their structures were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and UV spectra. Furthermore, compounds 5, 18, 21, and 22 exhibited weak protective activity for corticosterone-induced PC12 cells damage.

Coffee, tea, and cocoa in obesity prevention: Mechanisms of action and future prospects.

Obesity, a major public health problem, causes numerous complications that threaten human health and increase the socioeconomic burden. The pathophysiology of obesity is primarily attributed to lipid metabolism disorders. Conventional anti-obesity medications have a high abuse potential and frequently deliver insufficient efficacy and have negative side-effects. Hence, functional foods are regarded as effective alternatives to address obesity. Coffee, tea, and cocoa, three widely consumed beverages, have long been considered to have the potential to prevent obesity, and several studies have focused on their intrinsic molecular mechanisms in past few years. Therefore, in this review, we discuss the mechanisms by which the bioactive ingredients in these three beverages counteract obesity from the aspects of adipogenesis, lipolysis, and energy expenditure (thermogenesis). The future prospects and challenges for coffee, tea, and cocoa as functional products for the treatment of obesity are also discussed, which can be pursued for future drug development and prevention strategies against obesity.

The structures of two polysaccharides from Lepidium meyenii and their immunomodulatory effects via activating NF-κB signaling pathway.

Lepidium meyenii Walp., also known as the "Peruvian national treasure", is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii. The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6-α-D-Glc, while branches feature T-α-L-Ara, 1,5-α-L-Ara, and T-α-D-Glc attached to the O-6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6-ß-D-Gal, 1,3,6-ß-D-Gal with a few 1,3-ß-D-GlcpA-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3-ß-D-Gal, T-ß-D-Gal, T-α-L-Ara, 1,5-α-L-Ara, with trace amounts of 1,4-ß-D-Glc and T-ß-D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1ß, TNF-α, and IL-6 from RAW 264.7 cells at concentrations ranging from 50 µg/mL to 400 µg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB-α, p-IκB-α, p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.

An updated review of the genus Rhododendron since 2010: Traditional uses, phytochemistry, and pharmacology.

Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development.

Four undescribed pyrethrins from seeds of Pyrethrum cinerariifolium and their aphidicidal activity.

Four undescribed pyrethrins C-F (1-4) as well as four known pyrethrins (5-8) were isolated from seeds of Pyrethrum cinerariifolium Trev. The structures of compounds 1-4 were elucidated by UV, HRESIMS, and NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC and ROESY), among which the stereostructure of compound 4 was determined by calculated ECD. Furthermore, compounds 1-4 were evaluated for their aphidicidal activities. The insecticidal assay results showed that 1-4 exhibited moderate aphidicidal activities at the concentration of 0.1 mg/mL with the 24 h mortality rates ranging from 10.58 to 52.98%. Among them, pyrethrin D (2) showed the highest aphidicidal activity, with the 24 h mortality rate of 52.98%, which was slightly lower than the positive control (pyrethrin II, 83.52%).

Structural characterizations and α-glucosidase inhibitory activities of four Lepidium meyenii polysaccharides with different molecular weights.

Four polysaccharides (MCPa, MCPb, MCPc, MCPd) were obtained from Lepidium meyenii Walp. Their structures were characterized by chemical and instrumental methods including total sugar, uronic acid and protein content determination, UV, IR and NMR spectroscopy, as well as monosaccharide composition determination and methylation analyses. Four polysaccharides were a group of glucans with different molecular weights ranging from 3.12 to 14.4 kDa, and shared a similar backbone chain consisting of (1→4)-glucose linkages with branches attached to C-3 and C-6. Furthermore, bioactivity assay showed that MCPs had concentration-dependent inhibitory activity on α-glucosidase. MCPb (Mw = 10.1 kDa) and MCPc (Mw = 5.62 kDa) with moderate molecular weights exhibited higher inhibitory activity compared with MCPa and MCPd.

Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity of Ganoderma meroterpenoids.

Covering: 2018 to 2022Meroterpenoids found in fungal species of the genus Ganoderma and known as Ganoderma meroterpenoids (GMs) are substances composed of a 1,2,4-trisubstituted benzene and a polyunsaturated side chain. These substances have attracted the attention of chemists and pharmacologists due to their diverse structures and significant bioactivity. In this review, we present the structures and possible biosynthesis of representative GMs newly found from 2018 to 2022, as well as chemical synthesis and biological activity of some interesting GMs. We propose for the first time a plausible biosynthetic pathway for GMs, which will certainly motivate further research on the biosynthetic pathway in Ganoderma species, as well as on chemical synthesis of GMs as important bioactive compounds for the purpose of drug development.

Development of actein derivatives as potent anti-triple negative breast cancer agents.

Actein is a natural triterpenoid glycoside, isolated from the rhizomes of Cimicifuga foetida, which have been demonstrated to be potential in the treatment of breast cancer previously. Herein, we described the design and synthesis of a series of actein derivatives as anti-triple negative breast cancer (TNBC) inhibitors. Of which, the most promising derivative 27 exhibited significant inhibitory activity against human TNBC cell lines HCC1806 and MDA-MB-231, with IC50 values of 2.78 and 9.11 µM, respectively. Structure-activity relationships of actein derivatives were also discussed. Moreover, preliminary mechanism investigation revealed that 27 significantly inhibited cancer cell proliferation via cell cycle arrest at S phase. In addition, western blot analysis showed that the activation of MAPK signaling pathway might contribute to derivative 27 induced cell death. Overall, these results indicate that 27 has the potential to be developed as a lead compound and compounds with the actein scaffold are a promising novel class of inhibitors to treat TNBC.

Diverse meroterpenoids with α-glucosidase inhibitory activity from Ganoderma cochlear.

Three new meroterpenoids, cochlearins J-L (1-3) and three known meroterpenoids (4-6) were isolated from the fruiting bodies of Ganoderma cochlear. NMR (1H and 13C NMR, 1H - 1H COSY, HSQC, HMBC and ROESY), and HRESIMS were employed for the structure elucidation of new compounds. The stereostructures of 1-3 were confirmed by calculated ECD and optical rotation methods. Furthermore, compounds (+)-1, (-)-1, (+)-2, (-)-2, (+)-3, (-)-3, and 4-6 were evaluated for their α-glucosidase inhibitory activity. The results showed that compounds (+)-1, (-)-1 and (+)-2 exhibited stronger inhibition against α-glucosidase with IC50 values of 24.18 ± 1.98, 26.49 ± 3.20 and 29.68 ± 2.73 µM, respectively, compared to the positive control ursolic acid (49.65 ± 2.21 µM). The molecular docking experiments reveal that (+)-2 and (-)-2 had different binding mode with α-glucosidase, leading to their different inhibition.

Two new degrade triterpenoids from Buxus bodinieri Levl.

Two new degrade cycloartane triterpenoids, named buboditones A, B (1, 2), together with ten known alkaloids, cyclobuxoviridine (3), N-dimethylcycloxobuxovircine (4), cyclovirobuxine C (5), cyclovirobuxine A (6), cycloprotobuxine C (7), cycloprotobuxine A (8), cyclobuxoxazine (9), cyclobuxoxazine A (10), buxruguline B (11), irehine (12), were isolated from the leaves and stems of Buxus bodinieri Levl., The structures of compounds 1-2 were elucidated by 1 D and 2 D NMR spectroscopic methods including HSQC, HMBC, 1H-1H COSY, NOESY, as well as HRESIMS spectroscopic analysis.

Anti-Adipogenic Lanostane-Type Triterpenoids from the Edible and Medicinal Mushroom Ganoderma applanatum.

Our previous research has shown that lanostane triterpenoids from Ganoderma applanatum exhibit significant anti-adipogenesis effects. In order to obtain more structurally diverse lanostane triterpenoids to establish a structure-activity relationship, we continued the study of lanostane triterpenoids from the fruiting bodies of G. applanatum, and forty highly oxygenated lanostane-type triterpenoinds (1-40), including sixteen new compounds (1-16), were isolated. Their structures were elucidated using NMR spectra, X-ray crystallographic analysis, and Mosher's method. In addition, some of their parts were evaluated to determine their anti-adipogenesis activities in the 3T3-L1 cell model. The results showed that compounds 16, 22, 28, and 32 exhibited stronger anti-adipogenesis effects than the positive control (LiCl, 20 mM) at the concentration of 20 µM. Compounds 15 and 20 could significantly reduce the lipid accumulation during the differentiation process of 3T3-L1 cells, comparable to the untreated group. Their IC50 values were 6.42 and 5.39 µM, respectively. The combined results of our previous and present studies allow us to establish a structure-activity relationship of lanostane triterpenoids, indicating that the A-seco-23→26 lactone skeleton could play a key role in anti-adipogenesis activity.

Unusual ent-Kaurane Diterpenes from the Coffea Cultivar S288 Coffee Beans and Molecular Docking to α-Glucosidase.

A total of 11 new (1-11) and 2 known (12 and 13) ent-kaurane diterpene derivatives were identified from the roasted beans of Coffea cultivar S288. Their structures were established by extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance (heteronuclear single-quantum correlation, heteronuclear multiple-bond correlation, correlation spectroscopy, and rotating-frame Overhauser enhancement spectroscopy), high-resolution electrospray ionization mass spectrometry, and X-ray analyses. Cafespirone acid A (1) represents the first example of diterpene featuring a spirocyclic skeleton constructed from a 6/6/5 tricyclic system. Cafeane acid A (2) possesses a 6/6/6/5 tetracyclic system as a result of the C/D ring rearrangement. Furthermore, compounds 1-12 were evaluated for their α-glucosidase inhibitory activity. The results showed that compounds 2, 4, 5, 6, 7, 10, and 11 had a moderate inhibitory effect on α-glucosidase, and half-maximal inhibitory concentration values of compounds 4, 6, 7, and 10 were 18.76 ± 1.46, 4.88 ± 0.03, 12.35 ± 0.91, and 12.64 ± 0.59 µM, respectively, compared to the positive control acarbose (60.71 ± 16.45 µM). Additionally, the molecular docking experiments showed that the carbonyl group at C-19 of compounds 4, 6, and 7 formed strong hydrogen bonds with ARG315, which may make them have moderate inhibitory activity.

Flavonoid glycosides from the nectar of Camellia reticulata Lindl.

The nectar of Camellia reticulata Lindl. contains sugar, amino acids and other nutritional components, suggesting that it could be developed for food and food additives. To understand the effects of the nectar on human health, we investigated its chemical constituents. Two new flavonoid glycosides, cameretiins A and B (1 and 2), and two known flavonoid glycosides, kaempferol 3-O-(2''-O-E-p-coumaroyl)-ß-D-glucopyranoside (3) and tiliroside (4) were obtained from the nectar of Camellia reticulata Lindl. Their structures were determined based on analysis of their spectroscopic data and by comparison with 1D NMR spectroscopic data of known compounds reported in the literature. Compounds (1-4) were first isolated from the nectar of Camellia reticulata Lindl.

Two new triterpenoid-chromone hybrids from the rhizomes of Actaea cimicifuga L. (syn. Cimicifuga foetida L.) and their cytotoxic activities.

Two new triterpenoid-chromone hybrids, cimitriteromones H (1) and I (2), along with two known analogues (3, 4) were isolated from the phytochemical research on the n-butyl alcohol extracts of Actaea cimicifuga rhizomes. The new compounds were elucidated by spectroscopic experiments and chemical method. The cytotoxic activities of the isolated compounds were tested on A-549/Taxol cell line. Cimitriteromone I (2) showed cytotoxicity with IC50 value of 27.14 ± 1.38 µM comparable to positive control group cisplatin (IC50 value of 25.80 ± 1.15 µM).

FPR2-based anti-inflammatory and anti-lipogenesis activities of novel meroterpenoid dimers from Ganoderma.

Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC50 value of 7.93 µM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 µM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-ß (C/EBP-ß), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.

Morphological Changes and Component Characterization of Coffee Silverskin.

Nuclear magnetic resonance (NMR) spectroscopy was used for the qualitative and quantitative analysis of aqueous extracts of unroasted and roasted coffee silverskin (CS). Twenty compounds were identified from 1D and 2D NMR spectra, including caffeine, chlorogenic acid (CGA), trigonelline, fructose, glucose, sucrose, etc. For the first time, the presence of trigonelline was detected in CS. Results of the quantitative analysis showed that the total amount of the main components after roasting was reduced by 45.6% compared with values before roasting. Sugars in the water extracts were the main components in CS, and fructose was the most abundant sugar, its relative content accounting for 38.7% and 38.4% in unroasted and roasted CS, respectively. Moreover, 1D NMR combined with 2D NMR technology shows application prospects in the rapid, non-destructive detection of CS. In addition, it was observed by optical microscopy and scanning electron microscopy (SEM) that the morphology of CS changed obviously before and after roasting.

Functional triterpenoids from medicinal fungi Ganoderma applanatum: A continuous search for antiadipogenic agents.

Previously, we have demonstrated the antiadipogenic benefits of Ganoderma triterpenoids (GTs), which indicated GTs have potential therapeutic implications for obesity. In this study, the EtOAc extract of Ganoderma applanatum was further phytochemically investigated for searching new antiadipogenic agents, which led to the isolation of a total of 15 highly oxygenated lanostane triterpenoids, including 9 new compounds (1-9) and 6 known analogues (10-15). Structurally, ganodapplanoic acids A and B (1, 2) are two rearranged 6/6/5/6-fused lanostane-type triterpenoids with an unusual C-13/C-15 oxygen bridge moiety. In addition, the EtOAc extract (GAE) and isolates (1-4,6-15) were assayed for their antiadipogenic effects in 3T3-L1 adipocytes. The results revealed that compound 9 effectively repressed adipogenesis through down-regulating the expression of major proteins (PPARγ, CEBPß and FAS) involving differentiation and adipogenesis in 3T3-L1 adipocytes. Thus, the present study further demonstrated the antiadipogenic potential of GTs and provided a possible perspective for obesity treatment.

Lepipyrrolins A-B, two new dimeric pyrrole 2-carbaldehyde alkaloids from the tubers of Lepidium meyenii.

Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2­carbaldehyde alkaloids, lepipyrrolins A-B (1-2), seven pyrrole-alkaloid derivatives, macapyrrolins D-J (3-9), along with three known ones (10-12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1, 3-12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC50 value of 16.78 ± 0.49 µM.

Hydroxynitrile Glucosides: Bioactive Constituent Recovery from the Oil Residue of Prinsepia utilis.

The seed oil of Prinsepia utilis is extensively used as an edible oil by the nationalities of Naxi, Tibetan, and Mosuo in China, which is particularly good for beauty care and has a health protection function. A large amount of industrial waste is thrown away during the production process of seed oil. Therefore, to recover bioactive compounds from the oil residue of P. utilis is environmentally friendly and economically important. For this purpose, the chemical constituents of the P. utilis oil residue were investigated in our research, and five new compounds, prinsepicyanosides F-I (1-4) and prinamoside A (5), together with 16 known compounds (6-21) were isolated. The structures of the new compounds (1-5) were unambiguously confirmed by extensive spectroscopic techniques. Preliminary in vitro pharmacological studies showed that the hydroxynitrile glucosides (3, 9, and 10) exhibited weak α-glucosidase inhibitory activity. To a certain extent, our research provides some evidence for the pharmacological function of γ-hydroxynitrile glucosides and proposes new ideas for recycling of the oil residue of P. utilis.