Seven compounds, comprising three anthraquinones and four stilbenoids, were isolated from the roots of Rheum palmatum L. These compounds include chrysophanol (1), aloe-emodin (2), aloe-emodin 8-O-β-D-glucopyranoside (3), desoxyrhapontigenin (4), rhapontigenin (5), desoxyrhaponticin (6), and piceatannol 3'-O-β-D-glucopyranoside (7). Among these, compound 5 showed potent β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activity with an IC value of 0.256 ± 0.008 μM, making it the most effective inhibitor obtained from herbal extracts to date, followed by compounds 3 (1.164 ± 0.108 μM), 6 (1.213 ± 0.193 μM), 7 (1.270 ± 0.130 μM), and 4 (2.028 ± 0.108 μM). Furthermore, kinetic analysis revealed that compound 5 acted as a mixed type-I inhibitor with an inhibition constant K value of 0.28 ± 0.07 μM. Notably, compound 2 exhibited potent Aβ aggregation inhibition with an IC value of 3.56 ± 0.19 μM, whereas compound 5 showed low Aβ aggregation inhibition with an IC value of >40 μM. The docking simulations revealed that compound 5 had a high binding affinity and interacted with TYR132, predicting it as a key residue for inhibition via hydrophobic interaction, and with THR133 via hydrogen bonding, in the flap region of BACE1. These results suggest that stilbenoids generally exhibit higher BACE1 inhibitory activity than that of anthraquinones, and that compound 5 (rhapontigenin) could be a promising candidate for the treatment of Alzheimer's disease as a potent BACE1 inhibitor.

The roots of Shuteria involucrata (Wall.) Wight & Arn., known as "Tong-qian-ma-huang" in Dai folk medicine in China, are renowned for their efficacy in treating asthma. Despite the use of S. involucrata has been reported as ameliorating respiratory diseases, its mechanism of action remains unclear. This work described the effect of ethyl acetate extract of S. involucrate (SSE) on allergic asthma and its potential mechanism of action was assessed. Ovalbumin was used in vivo to establish a BALB/c asthma mouse model. Lipopolysaccharide was used in vitro to stimulate the human macrophage cell line THP-1 to establish an inflammatory model. In vivo and in vitro experiments showed that SSE effectively ameliorated pathological symptoms and attenuated airway inflammation and cellular inflammation in allergic asthma mice, with a mechanism of action potentially associated to the inhibition of the TLR4/NF-κB signaling pathway.

Rheumatoid arthritis (RA) is a prolonged autoimmune disease that targets the lining of small joints, causing inflammation and destruction of bone and cartilage. Anti-inflammatory drugs are available but offer short-term relief with adverse side effects. The present research was planned to study the in-vivo antiarthritic potential of ajugarin-I, sequestered from the Ajuga bracteosa. In-vivo studies include anti-inflammatory, analgesic, antidepressant, hematology profile, histopathological, radiological, and antioxidant analysis. The in-vivo results revealed that a high dose (HD, 60 mg/kg) of ajugarin-I significantly decreased the inflammatory paw edema (40 ± 0.04 %). Ajugarin-I also showed excellent analgesic behavior with 89 ± 0.55 % and 85 ± 0.55 % increments in pain threshold induced by cold and hot stimuli. Whereas ajugarin-I showed 95.1 ± 0.04 % antidepressant activity. Moreover, it showed strong antioxidant potential by raising the level of catalase, glutathione-S-transferase, and reducing glutathione while decreasing MDA levels in the liver, kidney, brain, paw, and spleen. Reduced serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) (with 67.5 ± 3.53 %, 83.5 ± 3.53 % and 85 ± 7.07 % respectively), were observed with HD of ajugarin-I. Furthermore, its 60 mg/kg dose restored hematological abnormalities by raising the Hb level (85 ± 0.7 %) RBCs (91 ± 0.5 %), MCV (83 ± 2 %), platelet count (83 ± 0.5 %) and lowered the WBC (68 ± 0.35 %) level. Abnormalities in histoarchitecture of paw, liver, and kidney were curtailed by HD of ajugarin-I demonstrating its regenerative properties. Radiological analysis of the left hind paw showed that ajugarin-I lessened the inflammation in articular areas. These findings will guide a novel area of research for exploiting ajugarin-I as novel anti-arthritic and anti-inflammatory agent.

Modified Shi Hui San (MSHS) has shown excellent therapeutic effects on ulcerative colitis (UC) patients clinically in China. However, the exact mechanism underlying its effect remains unclear and needs to further investigation.

Six new prenylated isoflavonoids, named maccosas A-F (1-6), together with ten known prenylated isoflavonoids (7-16) were isolated from the twigs and leaves of Maclura fruticosa. Compounds were isolated by various column chromatographic methods including silica gel, sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and comparison of their spectral data with those in the literature. Furthermore, compounds 1 and 7 exhibited anti-inflammatory activity with IC values of 4.11 and 1.45 μM. Detection of cellular pyroptosis and western blot assay suggested that compound 1 reduced the number of PI-positive cells and inhibited Nigericin-induced pyroptosis of J774A.1 cells.

Five novel coumarins (1-5) were isolated from the root of Notopterygium incisum, and their chemical structures were elucidated based on HRESIMS and NMR spectral data. The anti-inflammatory activities of compounds 1-5 were evaluated in a lipopolysaccharide-induced RAW 264.7 cell model by measuring the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). The results demonstrated that all five compounds exhibited significant anti-inflammatory potential. Further studies showed that compound 5 (at a concentration of 7.5-30 μM) displayed potent anti-inflammatory effects by inhibiting the expression of inflammatory mediators (COX-2, iNOS) and reducing nitric oxide (NO) production. Mechanistic studies revealed that compound 5 exerted its anti-inflammatory effects by inhibiting the NF-κB signaling pathway. These findings highlight the potential of coumarins as anti-inflammatory agents and provide a foundation for their further exploration as therapeutic candidates.

Current pharmacological treatments against diabetes do not reach optimal results in many conditions, and the attention of medicinal chemists is currently dedicated to multi-target compounds with antioxidant, anti-inflammatory and anti-diabetic properties. In this connection, medicinal plants represent valuable sources. Grandidentatin is a phenolic glycoside isolated from the leaves of Salix acmophylla Boiss., and in the current study its anti-inflammatory activity was investigated in vitro through red blood cells membrane stabilization and protein denaturation assays, and it was comparable to that of the positive control diclofenac sodium. Additionally grandidentatin was effective in the glucose uptake assay, used to assess the blood sugar lowering action, in the same concentration range of metformin. Computational studies were also enrolled to investigate the physico-chemical properties and the mechanism of action, showing that the molecule possesses the features to be defined as a "drug-like" compound, and that it may target aldose reductase as observed by docking studies.

Seven abietane diterpenoids (1-7) were isolated from the roots of Clerodendrum trichotomum, and the most abundant compounds, uncintone (1) and teuvincenone B (3), were subjected to structural modification to produce eleven derivatives (8-18). Their structures were elucidated using spectroscopic methods and quantum chemical calculations. The neuroprotective activities of these diterpenoids were assessed using HT22 cell models damaged by glutamate and acrolein. Most compounds exhibited promising neuroprotective effects against neuronal injury induced by these toxins at a concentration of 10 μM. These findings provide a promising basis for the further investigation of abietane diterpenoids as candidates in neuroprotective drug development.

This study aimed to explore the mechanisms of Feiyanning formula (FYN) on acute lung injury (ALI) using pharmacokinetics combined with network pharmacology strategy. Firstly, pharmacokinetic studies of 13 major bioactive components in normal and ALI mice were conducted using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Secondly, metabolomics was utilized to explore the metabolites affected by FYN. Finally, the network pharmacology was used to analyze the pharmacological mechanism of FYN's pharmacokinetic target components in ALI treatment, with western blotting (WB) experiment performed for verification. The pharmacokinetic results showed that compared to normal mice, the C and AUC of wogonin, oroxylin A, liquiritigenin, tetrandrine, and fangchinoline were significantly increased in ALI mice. The results of the lung tissue distribution showed that compared to normal mice, the AUC of wogonin and oroxyloside was significantly increased in ALI mice; the C of wogonoside and norwogonin was significantly increased in ALI mice. Metabolomics analysis showed that FYN may alleviate LPS-induced lung inflammation in mice by regulating related pathways including purine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis in both serum and lung tissue. Network pharmacology identified 110 overlapping genes between the 13 absorbed components and ALI-related targets. In KEGG enrichment analysis, the PI3K/AKT signaling pathway was identified as a significant pathway. WB experiment confirmed that FYN reduced the expression ratios of p-PI3K/PI3K, p-AKT1/AKT1, p-EGFR/EGFR, and TLR4 levels in lung tissue of ALI mice. This study might offer a solid foundation for evaluating the clinical efficacy of FYN.

Two new compounds, a benzofuran derivative (1) and a benzoate derivative (2), along with four known γ-pyrones (3-6), were isolated from the culture broth of Dentipellis fragilis. Their chemical structures were elucidated via spectroscopic analysis. The anti-inflammatory and cytotoxic effects of these compounds were assessed. Compound 4 exhibited significant anti-inflammatory activity, inhibiting approximately 60 % of NO production at 0.005 μM without cytotoxic effects. Additionally, compound 2 showed moderate cytotoxicity against HCT-116 and Mia Paca-2 human cancer cells, with IC values.

Landolphia genus is known in West Africa for its various ethnomedicinal uses. Therefore, the lianas of Landolphia violaceae (Apocynaceae) were investigated to characterize/identify its chemical constituents as well as the antioxidant activities and toxicity of samples. The investigation of the AcOEt extract of this plant led to the isolation of three previously unknown compounds named: landolphioside A (1), landolphioside B (2) and landolphioside C (3) along with 5 known compounds. Their structures were determined on the basis of their spectroscopic data. 1 and 2 represent rare flavonoids with a C-benzylcarbonyl group on ring A identified from Apocynaceae family. The free radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), the Total Reducing Power (TRP) assay and the Total Antioxidant Capacity (TAC) were carried on the AcOEt extract and the isolates 1-4 and 6. The toxicity of the extracts was investigated through Brine Shrimp Lethality Assay (BSLA). The AcOEt extract displayed a high total antioxidant capacity corresponding to 218.81 ± 0.17 mg/g of dried extract (ascorbic acid equivalent) and demonstrated significant DPPH free radical scavenging activity (IC = 12.81 ± 0.21 μg/mL). Else, it appeared relatively toxic (greater than 80 % at 200 μg/mL) against brine shrimp lethality (Artemia salina), when compounds 3, 4 and 6 showed high to moderate toxicity with LC values (in μM) of 87.82, 139.18 and 336.44 respectively. These results highlighted the plausible medicinal use of L. violaceae which henceforth can be considered as a source of potent bioactive compounds, with presumably antioxidant and moderate toxic effects.

Three new protolimonoids, entandrophins A-C (1-3), together with two known compounds, methyl angolensate (4) and stigmas-4-en-3-one (5), were isolated from the bark of Entandrophragma angolense. Their structures were elucidated based on spectroscopic analyses, mainly 1D and 2D NMR spectral data. The compounds were evaluated for their cytotoxicity against HepG2 cells and α-glucosidase inhibitory activity. Compounds 1-4 displayed very weak activity against HepG2 cells but compounds 2 and 3 exhibited significant α-glucosidase inhibition with IC values of 57.5 ± 1.5 and 32.5 ± 0.9 μM, respectively.

()-(7S,8S)-10,11-dihydro-curcumene-3,8-diol (1) and one new cadinane-type sesquiterpenoid, ()-(1R,4S,6S,7S,10R)-cadinan-1,4-diol (2), together with six known ones (3-8), were isolated from 95 % ethanol extract of the heartwood of Entandrophragma cylindricum. Structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and quantum chemical calculations, including GIAO calculation of NMR chemical shifts and TDDFT calculation of ECD spectrum, which verified the relative and absolute configurations on the flexible side chain of 1, respectively. All sesquiterpenoids were evaluated for their potential to enhance glucose uptake in C2C12 myotubes. Compound 2 (20 μM) significantly increased glucose uptake to the same level as that of metformin (2 mM). Western blot analysis on AMPKα, GLUT4, and ACC1 revealed that compound 2 activated the AMPK-GLUT4 signaling pathway in C2C12 myotubes.

Natural products are an important source of drug candidates against fatty liver. Herein, two previously undescribed monocyclic polyprenylated acylphloroglucinols (MPAPs, 1 and 2) and three new polycyclic polyprenylated acylphloroglucinols (PPAPs, 3-5) were isolated from the pericarps of Garcinia multiflora, and structurally elucidated by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) calculations, together with five known PPAPs. Compounds 1 and 2 are rare dinor-MPAPs. In lipopolysaccharide (LPS)-induced RAW264.7 macrophages, compounds 1, 3 and 4 significantly suppressed nitric oxide production. Among them, compound 3 showed the best inhibitory effect with an IC value of 4.12 ± 0.94 μМ. Furthermore, compound 3 effectively reduced interleukin-1β secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. Interestingly, the conditioned medium from LPS plus nigericin-stimulated THP-1 macrophages pre-treated with compound 3 attenuated lipid accumulation in oleic acid plus palmitic acid (2/1)-induced HepG2 hepatocytes. Taken together, these findings expand the chemical diversity of G. multiflora, and further demonstrate the potential of PPAPs as candidates for treating steatohepatitis.

Vaginal dysbiosis (VaD) is a common issue among menopausal women, who are particularly susceptible to cardiovascular disease (CVD). Pterocarpus sp. are known to induce estrogen-like activities, which are the key pathways for menopause-related disorders. This study aims to evaluate the potential of Pterocarpus mildbraedii water extract on VaD and CVD risk factors using an estropause (EP) rat model. Furthermore, predictive ADME properties and molecular docking with target proteins were assessed to develop alternative medicinal treatments for menopause. The secondary metabolites in P. mildbraedii water extract (Pm) were analyzed using UHPLC-MS and quantitative phytochemistry methods. The extract's ability to scavenge free radicals was evaluated using DPPH, ABTS, and FRAP tests. Molecular docking assessed the extract's binding ability to various receptors. SwissADME and Molinspiration were utilized to predict its pharmacokinetic and bioactivity properties. Subsequently, the therapeutic potential of Pm was assessed in rats, focusing on its estrogen-like, eubiotic, and cardioprotective activities. UHPLC-MS enables us to identify several compounds. Predictive ADME analyses have indicated that most compounds comply with Lipinski's Rule of Five for oral drugs. Additionally, they inhibit CYP1A2 and bind to several receptors and enzymes through conventional hydrogen bonding. In rats, ovariectomy-induced EP reduced glycogen levels and vaginal lactic acid and decreased in the population of Lactobacillus spp., which is characteristic of VaD. This condition also increases CVD risk factors. Overall, this study underscores the potential of Pterocarpus mildbraedii in preventing VaD and CVD risk factors related to hypoestrogenism. This extract positions itself as a promising alternative treatment for menopause-related disorders.

The plant family Iridaceae is a rich source of structurally rare iridal-type triterpenoids. In this study, we investigated the structural diversity of iridal triterpenoids contained in the rhizome of Iris domestica using metabolomics-based molecular networking. Guided by MS features of iridal triterpenoids obtained from LC-MS-based molecular networking, two new aliphatic fatty acid ester-bearing monocycloiridal type triterpenoids, named as 16-acetyliridal A (1) and 16-acetyliridal B (2), as well as a known compound (3), were isolated from the rhizomes of I. domestica. The structures of new compounds were elucidated based on the HR-ESIQTOFMS, MS fragmentations, and NMR spectroscopy. Compound 2 is the first example of iridal-type homotriterpenoids featuring an unusual acyl moiety at a cyclohexane ring instead of a formyl group that is commonly shared in the iridal triterpenoids. All isolated compounds exhibited a high potency to promote neurite outgrowth activities with or without the supplementation of nerve growth factor on PC12 cells in a dose-dependent manner.

Four new meroterpenoids, including two seco isodhilarane-type meroterpenoids peniciacetals J-K (1 and 2), two austins-type meroterpenoids peniciacetals L-M (3 and 4), along with five known analogues (5-9) were isolated from the mangrove-derived fungus Penicillium sp. HLLG-122 based on the OSMAC approach. The structures, including absolute configurations of new compounds were elucidated by HRESIMS, 1D, 2D NMR spectroscopic data, X-ray diffraction analysis, and quantum chemical electronic circular dichroism (ECD) calculation. Peniciacetal J (1) was characterized with a unique 6/7/6/5/6/5 hexacyclic systems with a furan ring moiety. Compound 3 showed weak cytotoxicity against HepG2 and MCF-7 cell lines with IC values of 38.9 and 34.1 μM, respectively. Compound 8 showed moderate cytotoxicity against HepG2 and MCF-7 cell lines with IC values of 10.7 and 13.3 μM, respectively. Compound 9 exhibited good cytotoxicity against HepG2 cell line with the IC value of 4.8 μM.

Two undescribed ten-membered lactones, named penicirestricols A (1) and B (2), and two unprecedented ten-membered lactone-adenine hybrids, penicirestricols C (3) and D (4), along with four known compounds, decarestrictines B (5), A (6), F (7), and I (8) were isolated from the endophytic fungus Penicillium restrictum. The structures were determined by 1D, 2D NMR techniques, mass spectrometry, ECD, and NMR calculations. Compounds 3, 7, and 8 from P. restrictum showed significant antifungal activities against postharvest pathogens Fusarium asiaticum and Alternaria tenuissima with MICs ≤8 μg/mL. Thus, the compounds isolated from P. restrictum have the potentiality to be developed as the novel antifungal agents.

Seven undescribed cassane diterpenes, caeslpulrins A-G (1, 3, 4, and 6-9), the C-12 ethoxy derivatives of caeslpulrins A and C (2 and 5), along with five artificial or known cassane diterpenes (10-14) and eight known sesquiterpenoids (15-22) were isolated from the fruits of Caesalpinia pulcherrima. Their structures were elucidated by extensive spectroscopic analyses, including HR-ESI-MS, 1D and 2D NMR, and electronic circular dichroism (ECD) calculations. Caeslpulrins A-F were identified as a group of rare cassane butenolides possessing a C-3 benzoyloxy unit. This is the first report of a series of such cassane diterpenes from a Caesalpinia plants. Compounds 1-7 were evaluated their inhibitory effects on NO production in the LPS-induced RAW 264.7 macrophages, and their cytotoxicities against several human tumor cell lines using MTS method.

Five new alkaloids, ferupencines A-E, featuring a pyrrol-oxazine core with a C- CON framework, were isolated from the secondary metabolites of the endophytic fungus Penicillium sizovae residing in Ferula sinkiangensis. Their structures were elucidated through comprehensive 1D and 2D NMR spectroscopy, along with mass spectrometric analysis, experimental and calculated (ECD) spectra, and other complementary methods. The absolute configuration of compound 1 was determined via X-ray crystallography, supported by experimental and calculated electronic circular dichroism (ECD) data. Notably, this is the first report of these compounds being isolated from endophytic fungi. The cytotoxicity of ferupencines A-E (1-5) was evaluated against three human tumor cell lines: HeLa, SGC-7901, and SHG-44. Compound 2 exhibited moderate cytotoxic activity against HeLa and SGC-7901 cells, with IC values of 18.6 μM and 14.2 μM, respectively. Additionally, compound 5 showed an IC value of 23.8 μM against HeLa cells, indicating moderate cytotoxic potential.

Eight new C-steroidal glycosides (1-8) and fourteen known analogs (9-22) were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae). The structures of the new compounds elucidated on the basis of their IR, HR-ESI-MS, and NMR data. The cytotoxicities of compounds 1-22 were evaluated against two prominent human cancer cell lines, SW480 and MDA-MB-231, leading to a preliminary structure-activity relationships (SARs). Notably, compounds 1, 5, 8, 10, and 22 exhibited significant cytotoxic activity against both cell lines, with IC values ranging from 8.76 ± 1.36 to 17.90 ± 1.77 μM for SW480 and from 10.97 ± 1.73 to 12.07 ± 1.13 μM for MDA-MB-231.