QiShenYiQi dripping pills ameliorate post-myocardial infarction cardiac fibrosis via modulation of the cAMP/Rap1 and PI3K/Akt signaling pathways
Myocardial infarction (MI) is a multifactorial cardiovascular condition characterized by metabolic disturbances and inflammatory responses. QiShenYiQi dropping pills (QSYQ), a traditional Chinese medicine formula, have shown therapeutic potential through multi-component and multi-target mechanisms, yet their effects from the perspective of active compounds and metabolites remain underexplored. This study utilized phytochemical characterization, metabolomics, network pharmacology, molecular docking, and biological validation to investigate QSYQ's pharmacological mechanisms in MI treatment. Chemical constituents were identified via UHPLC-Q-Orbitrap HRMS, and plasma metabolites from MI rats were analyzed using UPLC-MS/MS. Network pharmacology and docking revealed 19 active components, 68 target proteins, and key pathways, including cAMP-Rap1 and PI3K-Akt, associated with QSYQ's effects. Experimental validation demonstrated that QSYQ significantly improved cardiac function, reduced myocardial fibrosis, and modulated key pathway proteins, including Cyclin D1. A two-week regimen proved more effective than one week. Enrichment analysis highlighted QSYQ's role in regulating cell proliferation and survival, supported by changes in 45 plasma metabolites. Molecular docking confirmed interactions between active components and targets, and biological validation reinforced the importance of cAMP-Rap1 and PI3K-Akt pathways. This study provides a systematic framework for understanding the therapeutic mechanisms of QSYQ, emphasizing its potential in addressing cardiac dysfunction and myocardial fibrosis in MI.
Corrigendum to "Bushen Yinao pill improves cognitive function in Alzheimer's disease rats by regulating PI3K/Akt pathway and intestinal microbiota" [Fitoterapia 188 (2026) 106999]
Four new resin glycosides, calyjaponins I-IV, from the aerial parts of Calystegia japonica
Calystegia japonica Choisy (Convolvulaceae) is a perennial herbaceous vine widely distributed throughout southeastern and eastern Asia. In traditional Chinese medicine, the whole parts of C. japonica have been used for their diuretic and tonic properties. In this study, four new resin glycosides, designated calyjaponins I (1)-IV (4), were isolated from the aerial parts of C. japonica. Their structures were elucidated on the basis of spectroscopic data and chemical analyses. All compounds possessed new glycosidic acid moieties and were identified as hexaglycosides featuring intramolecular cyclic ester (jalapin-type) structures, in which the sugar moieties were partially acylated with organic acids, including (E)-2-methylbut-2-enoic and 2R-methyl-3R-hydroxybutyric acids. Compounds 1-4 were further evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and for cytotoxicity against HL-60 human promyelocytic leukemia cells. All tested compounds exhibited both anti-HSV-1 and cytotoxic activities.
Effects of nutritive and non-nutritive sweeteners on acne vulgaris: A systematic review
Acne vulgaris is a prevalent inflammatory skin disorder influenced by sebaceous gland activity, hormonal regulation, and microbial proliferation. Dietary factors, including sweetening agents, may modulate acne pathophysiology, affecting sebum production, inflammatory responses, and the skin microbiome. This systematic review summarizes the effects of nutritive and non-nutritive sweeteners on acne-related markers, with a focus on Cutibacterium acnes activity and associated inflammatory pathways. Non-nutritive sweeteners such as mannitol and xylitol show potential in regulating acne pathogenesis and exhibiting antibacterial activity against C. acnes. Strategic combinations of sweeteners with bioactive compounds, such as mannitol with bakuchiol or Ginkgo biloba extract, and xylitol with propanediol and caprylic acid, further enhance anti-inflammatory and antimicrobial effects, offering a multifaceted approach to acne management. For nutritive sweeteners, experimental evidence suggests that glucose may enhance C. acnes biofilm susceptibility when combined with certain antibiotics. These findings emphasize the importance of careful selection and formulation of sweetening agents in dermatological interventions. Incorporating sweeteners, alone or in combination with bioactive compounds, could complement conventional acne therapies, reduce microbial proliferation, modulate inflammatory pathways, and support overall skin health. This review provides a scientific basis for dietary recommendations and the development of adjunctive acne treatments, highlighting sweetening agents as emerging functional modulators of acne pathogenesis.
Study on chemical constituents and their biological activities from the stems of Syringaoblata Lindl
This study investigates the chemical constituents and biological activities of the stems of the Mongolian medicinal plant Syringa oblata Lindl. ("Alashan-Agaru"). Through chromatographic separation and spectroscopic analysis, 34 compounds were isolated from the ethyl acetate fraction, including four new and ten first-reported in Syringa species. Using an LPS-induced RAW264.7 macrophage model, several compounds significantly inhibited NO production. It is known that compound 34 significantly reduced the levels of interleukin - 1β, interleukin - 6 and CD14. In addition, among the 23 lignans detected by the DPPH method, five showed strong antioxidant activity, with half - maximal inhibitory concentration (IC₅₀) values lower than that of vitamin C. These results provide a scientific basis for the medicinal use of the stems of Syringa reticulata var. amurensis.
Sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-renal fibrosis activities
Six new sesquiterpenoids, including two cadinane sesquiterpenoids (1 and 2), four eudesmane sesquiterpenoids (3-6), together with seven known analogues (7-13) and two diphenylheptanes (14 and 15) were isolated from the fruits of Alpinia oxyphylla. The structures of these new compounds were elucidated by analysis of spectroscopic data (NMR) and electronic circular dichroism (ECD) calculations. The cell viability and anti-renal fibrotic activity of compounds 1-6 were analyzed by CCK-8 and Western blotting, and compounds 2 and 6 exhibited inhibitory renal fibrosis activity in TGF-β1-induced renal proximal renal tubular cells, and dose-effect relationships were observed in compounds 2 and 6.
Oligosaccharide esters from Polygala paniculata with their NO inhibitory activity
Polygala paniculata L. has been reported to exhibit diverse therapeutic effects, including neuroprotective, gastroprotective, antinociceptive, antidepressant, vasorelaxant, and hypotensive effects, as well as traditional uses in treating stomachache, rheumatic pain, rhinitis, and chronic bronchitis. Using multiple chromatographic techniques, 10 oligosaccharide esters were isolated from the whole plants of P. paniculata, comprising seven new compounds, polypanicoses A-G (1-7), one new natural product, 3'-O-benzoylsucrose (8), and two known ones, senegose F (9) and tenuifoliside A (10). Their structures were elucidated through comprehensive spectroscopic methods, including NMR and HRESI mass spectra. Compounds 1-6, 8, and 9 inhibited nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with IC values ranging from 44.6 ± 1.0 to 99.6 ± 8.3 μM. Molecular docking simulations suggested that 1 and 4 inhibit NO overproduction by binding to the active site of iNOS, thereby modulates the protein's activity. Both 1 and 4 further attenuated iNOS expression, suggesting that their NO inhibitory activity is associated with down-regulation of iNOS expression.
The mechanistic role of Poria cocos in cancer treatment: Antitumor activity and adjuvant potential in chemotherapy
Poria cocos is a prominent traditional fungal medicine that has been utilized in China for over a millennium. Its major bioactive constituents include triterpenes and polysaccharides, along with other minor components such as steroids, histidine, choline, amino acids, and essential minerals, which exhibit diverse pharmacological mechanisms, including antitumor, antibacterial, immunomodulatory, anti-aging, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, and cardioprotective effects. Globally, cancer remains a leading cause of mortality, accounting for approximately nine million deaths annually. Despite advances in current conventional therapies, complete tumor eradication remains elusive, and these treatments are often accompanied by severe adverse effects. To comprehensively evaluate the therapeutic potential of poria cocos, publications from 2002 to 2025 were systematically reviewed from PubMed, Web of Science, ScienceDirect, and Google Scholar. This review elucidates the antitumor properties of poria cocos on various cancers, including lung, colorectal, breast, and gastric cancers. Furthermore, it highlights its adjuvant role in enhancing the efficacy of chemotherapeutic agents through multiple mechanisms, such as inhibition of cellular proliferation and metastasis, induction of apoptosis and cell cycle arrest, and modulation of immune, inflammatory, and oxidative signaling pathways. Collectively, these findings demonstrate the promising antitumor and adjuvant potential of poria cocos in cancer therapy. Nevertheless, further investigations are required to determine optimal dosages, toxicity profiles, and clinical efficacy. Rigorous quality control, standardization, and well-designed clinical trials are essential to validate its safety and effective clinical application.
Dimeric Phthalides from an endophytic fungus Phomopsis sp. of Aconitum carmichaeli
Three racemic pairs of new dimeric phthalides, (±)-phomophthalides A-C ((±)-1-3), together with eight known compounds (4-11), were obtained from the culture broth of the endophytic fungus Phomopsis sp. YM 355364 isolated from the medicinal plant Aconitum carmichaeli. The chemical structures of the new compounds were established by extensive NMR spectroscopic and HRESI-MS analysis and DP4+ calculations. The new compounds were tested for their antimicrobial activities by broth microdilution method. Compound 1 showed moderate inhibitory activity toward three pathogenic fungal strains Fusarium solani, Candida albicans, and Botrytis cinerea with MIC values of 16, 32, and 32 μg/mL, respectively. Compound 2 exhibited antifungal activity against B. cinerea and C. albicans with MIC values of 16 and 32 μg/mL, respectively.
Anti-androgenic compound Embelin ameliorates polycystic ovary syndrome by reversing the ovarian dysfunction and associated metabolic irregularities in 5α-DHT-induced PCOS rats
We could successfully reverse the polycystic ovary syndrome (PCOS) in a rat model using an anti-androgenic compound extracted from Embelia tsjeriam-cottam, which exhibited spectral characteristics consistent with Embelin. The identity of the anti-androgenic fraction was confirmed as Embelin using FT-IR, UV spectrophotometry, and UPLC-MS/MS analyses. The anti-androgenic activity of the extracted Embelin was evaluated using the Yeast RIKILT Androgen Assay and compared against (i) 5α-dihydrotestosterone (5α-DHT), (ii) a commercially sourced Embelin standard, and (iii) flutamide, a known androgen receptor antagonist. In silico molecular docking studies further revealed that Embelin exerts its anti-androgenic effects by competitively binding to the ligand-binding domain of the androgen receptor (AR), with interaction energy values comparable to those of 5α-DHT and hydroxyflutamide. The embelin fraction (up to 100 μl) and in combination with 5α-DHT, was non-toxic and promoted normal cell proliferation in vitro. Further, the extract also efficiently scavenged the 5α-DHT-induced Reactive Oxygen Species generation and downregulated the 5α-DHT-induced androgen receptor (AR) expression significantly in the in vitro system. A PCOS rat model was successfully established through 5α-DHT induction. Embelin treatment effectively reversed several hallmark features of PCOS, including ovarian dysfunction (e.g., hypo-progesteronemia, follicular cysts, and estrous cycle irregularities) as well as metabolic disturbances such as insulin resistance, weight gain, dyslipidaemia, and adipocyte hypertrophy. In conclusion, this is the first study to demonstrate the therapeutic potential of Embelin in ameliorating PCOS-related ovarian and metabolic dysfunctions.
Pharmacological insights on multifaceted therapeutic applications of stilbenoids: A comprehensive updates
Stilbenoids are naturally existing phenolic chemicals that have a stilbene backbone structure and are found in a variety of plant species. Plants produce these antimicrobial substances, known as phytoalexins, in reaction to stresses such as disease or ultraviolet light. The structure, variety, isomer form, and biosynthesis of stilbenoids are important characteristics. In addition to their anti-inflammatory and anti-diabetic qualities, they also exhibit antibacterial activity, cardioprotective and neuroprotective benefits, and the ability to prevent and treat cancer. The most researched stilbenoid is resveratrol, although related substances such as piceatannol, gnetol, and pterostilbene also have notable bioactivity. In vitro, in vivo, and a few human clinical investigations have all been done on stilbenoids. Although preclinical models show promising results, further clinical data is required to validate their good benefits in people. To completely grasp their therapeutic potential, more investigation is required. This article explores naturally occurring stilbenoids and their therapeutic properties, including preclinical and clinical research, patents, and emerging research. It highlights their abundance, structural traits, bioavailability, safety, and effectiveness. This article also focus on polymeric carriers, such as nanoparticles, micelles, hydrogels, and dendrimers, improve the stability, bioavailability, and therapeutic efficacy of stilbenoids, polyphenolic compounds with multifaceted therapeutic applicationssuch as antioxidant, anti-inflammatory, anti-aging, cardioprotective, anti-diabetes, neurodegeneration, anti-obesity, anticancer, and antimicrobial properties.
Protective effect of Maren-Tiaogan Decoction on high-fat diet-induced MASLD in mice
Recent epidemiological studies have highlighted a significant increase in the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). This study explores the hepatoprotective mechanisms of Maren-Tiaogan Decoction (MRTGD), a traditional Chinese medicine (TCM) formulation, using a high-fat diet (HFD) murine model of MASLD. The findings may provide a safer and more effective TCM-based therapeutic option for patients with MASLD.
Integrating mouse oral trial, LC-HRMS-based untargeted metabolomics and network pharmacology for screening bioactive components of Astragalus membranaceus curing type-II diabetes mellitus (T2DM)
Astragalus membranaceus (AM), a well-known traditional Chinese medicine (TCM), has been found to exhibit significant therapeutic effects on T2DM. The mechanism of AM (root) extract ameliorating diabetes and its medicinal components were deep inverstigated in this work. A mouse oral trial, LC-HRMS-based untargeted metabolomics, quantitative spectrum effect relationship analysis (QSERA), and network pharmacology was integrated for this studying. With the aid of data-mining by AntDAS (Automatic Data Analysis Strategy) platform, 59 bioactive compounds involved in the Leprdb/db mouse model of T2DM therapy were screened from LC-HRMS fingerprints of AM (root) extract even in the presence of heavily interfered background. The key bioactive AM (root) metabolites, astragaloside and i-arabinose, influence T2DM targets including IL2 and HSP90AA1. Molecular docking experiment revealed high-affinity binding between astragaloside and i-arabinose and these core targets. QSERA predicted the specific regulatory effects of bioactive compounds on T2DM in mice. This integrated approach provides a novel strategy for interpreting the pharmacodynamic effects of AM (root) extract in T2DM, which may facilitate the clinical application of traditional Chinese medicine.
Indole diketopiperazine-based hybrids with dual TDP1 and TDP2 inhibitory activities from marine fungus aspergillus sp. EGF 15-0-3
Seven indole diketopiperazine-based hybrids, including four new compounds (1-4) and three known ones (5-7), were successfully isolated from the fungus Aspergillus sp. EGF 15-0-3. Comprehensive spectroscopic analyses, combined with single-crystal X-ray diffraction and electronic circular dichroism calculations, were employed to elucidate their structures, relative configurations, and absolute configurations. Biological evaluation revealed that all obtained compounds except 2 exhibited potential TDP1 inhibitory activity. Notably, compound 3 demonstrated unique dual inhibitory effects against both TDP1 and TDP2, highlighting its promising therapeutic potential.
Bioprospecting and exploration of the chemical profile of Lasiodiplodia sp. extracts: Evaluation of specialized metabolites by similarity calculations, and dereplication with differential H NMR
Endophytic fungi are well known for producing a wide variety of specialized metabolites, often characterized by complex and diverse chemical structures. In this study, the differential H NMR technique was used as an innovative tool for dereplication and for supporting compound identification in complex mixtures, complemented by similarity calculations developed to evaluate the similarity of the chemical profiles of the extracts obtained over consecutive cultivation days of Lasiodiplodia sp. One-dimensional (1D) and two-dimensional (2D) NMR analyses of the POLd-14 extract and MLd-1 to MLd-3 subfractions led to the identification of known compounds: 3-carboxy-2-methylene-4-heptanolide (1) and decumbic acid (2) in POLd-14; indole-3-carboxylic acid (3) in MLd-1 and MLd-3; 4-hydroxybenzoic acid (4) and 4-hydroxymellein (5) in MLd-1; and 4-hydroxyphenylacetamide (6) in MLd-2. Differential H NMR enabled the unequivocal identification of compounds (1) and (2). These results contribute to bioprospecting and to a better understanding of the metabolite diversity of Lasiodiplodia sp. under varying culture conditions, including diferences in carbon and nitrogen sources, cultivation periods, and extraction methods. The study also underscore the potential of Lasiodiplodia sp. endophyte as an alternative source of bioactive metabolites with pharmacological relevance, which can be cultivated under different conditions guiding the production of different specialized metabolites.
Multi-omics integration reveals that KLF improves stomach heat syndrome through intestinal flora remodeling and PI3K-Akt pathway activation
Stomach heat syndrome (SHS) is a common clinical digestive system disease, which seriously affects people 's quality of life. Kouchi Liuxiang Fang (KLF) has a significant effect in the clinical treatment of SHS. However, its potential therapeutic mechanism is not fully understood. The purpose of this study is to explore the potential mechanism in improving SHS by integrating multi-omics through network pharmacology. The in vitro and in vivo components of KLF were identified by UHPLC-Orbitrap Exploris/MS technology. Network pharmacology was used to predict the potential core pathways of KLF to improve SHS. The protective effect of KLF on SHS-induced gastric mucosal injury was evaluated in vitro and in vivo. Finally, the multi-omics strategies of network pharmacology, 16S rRNA sequencing and metabolomics were integrated to explore the mechanism of KLF in improving SHS. UHPLC-Orbitrap Exploris/MS identified 117 chemical components and 53 prototype components in KLF. In vitro and in vivo experiments showed that KLF had a good protective effect on SHS. Integrated multi-omics analysis (network pharmacology, 16S rRNA sequencing, metabolomics) revealed KLF improves SHS by restoring gut flora balance and activating the PI3K-Akt pathway, confirmed by Western Blot and RT-qPCR analysis. This study provides a basis for the mechanism of KLF in improving SHS, and provides a solid foundation for drug development and clinical application of SHS prevention and treatment.
The Tetradium ruticarpum-Zingiber officinale Roscoe herb pair inhibits atherogenic events: A study of the synergistic effects and active ingredient combination of a two-herb formula
The Tetradium ruticarpum (E)-Zingiber officinale Roscoe (Z) herb pair is a well-known herbal formulation with multiple beneficial cardiovascular pharmacological activities. Therefore, E and Z are potentially natural products for Atherosclerosis (AS). However, it is not clear whether E and Z work synergistically in the treatment of AS and which of their components is responsible. This study was to determine the synergistic effect of E and Z in the treatment of AS, to identify the active ingredient combination (AIC) that exerts the action of the original formula and to determine its molecular mechanism. First, the combined effects of E and Z were assessed in an ApoE mouse model and then confirmed in vascular smooth muscle cells (VSMCs) by the combination index (CI). In addition, the AIC of E-Z was evaluated by cascade analysis and its efficacy was confirmed in vitro and in vivo. The results showed that both E, Z and E-Z had anti-AS effects in ApoE mice, with E-Z having the most significant effect. Moreover, the CI method demonstrated that E, Z could synergistically inhibit the proliferation of VSMCs. In addition, the AICs obtained by the cascade analysis strategy effectively inhibited VSMCs proliferation in vitro and significantly reduced the formation of neoplastic endothelium in mice in vivo. This inhibitory effect was associated with the reduction of ROS levels and activation of the Nrf2/HO-1 signaling pathway in VSMCs. This study provides an effective method for characterizing herbal combinations, exploring their active ingredients, and promoting efficacy-based herbal quality control.
Phytochemical diversity, extraction techniques, and therapeutic potential of Erica species
This review systematically examines the scientific literature on the genus Erica (heathers), with a focus on their phytochemical diversity and pharmacological potential. The objective is to critically analyze how extraction methods and species origin influence the profiles of bioactive compounds responsible for therapeutic effects. A comprehensive evaluation of phytochemical data is presented for widely studied species, including Erica arborea, Erica andevalensis, Erica australis, Erica manipuliflora, Erica cinerea, Erica verticillata, Erica carnea, Erica scoparia, Erica spiculifolia, Erica multiflora, and Erica mannii. Evidence indicates that extraction techniques and solvent polarity strongly affect the yield and diversity of secondary metabolites such as phenolic acids, flavonoids, and terpenoids, which are associated with antioxidant, anti-inflammatory, antimicrobial, diuretic, and anticancer activities. Importantly, this review highlights pronounced taxonomic and geographic sampling biases: most studies focus on European and Mediterranean Erica species, with very limited representation from Africa despite its exceptional species richness. These findings emphasize the need to optimize extraction protocols and expand research to underrepresented taxa. Overall, this synthesis underscores the therapeutic promise of Erica species and provides a foundation for future drug discovery efforts guided by phytochemical characterization and bioactivity screening.
Phthalide compounds from the roots of Angelica sinensis and their blood-replenishing bioactivities
To investigate the blood-replenishing constituents from the roots of Angelica sinensis (Oliv.) Diels. The components were separated and purified by various chromatographic methods, and identified by physicochemical characterization and spectral data. The nitric oxide (NO) inhibition rate and mRNA expression of IL-6, IL-1β, TNF-α in LPS-induced RAW264.7 were detected by Griess method and RT-qPCR assays, respectively. The hemoglobin expression promotion rate in K562 cells was evaluated by benzidine staining method. Three new phthalide compounds (1-3), named as 7-(2-butyrylbenzoyl)senkyunolide I, 2-propyl-6,7-dioxolanesenkyunolide H, 6',7'-dicarboxyl-wallichilide, were isolated from root of A. sinensis together with 45 known compounds (4-48). Among them, the IC values for NO inhibition of 7-(2-butyrylbenzoyl)senkyunolide I (1), 7-acetylsenkyunolide H (5), angeolide (25), ligustchuane B (33) and dibutyl phthalate (36) were 3.43 μM, 3.77 μM, 3.92 μM, 3.23 μM and 3.93 μM, respectively. Ferulic acid (28), 4,8-dihydroxyacetophenone (38) and vanillic acid (48) showed good hemoglobin-promoting effects, with the promotion rate of 40.6 %, 33.4 %, and 37.8 %, respectively. Thus, A. sinensis exhibited the blood-replenishing bioactivities through a synergistic effect with phthalide and ferulic acid derivatives.
Hemolytic, antitumor, and antifungal activity of Eugenia gracillima Kiaersk. essential oil against Candida glabrata: In vitro and in vivo evaluation
Eugenia gracillima Kiaersk. is traditionally used in the treatment of urinary tract infections, respiratory disorders, and skin conditions, and its essential oil (EgEO) from leaves has shown antioxidant, anti-protozoal, analgesic, and anti-inflammatory effects, although its pharmacological potential remains insufficiently studied. This work aimed to evaluate the hemolytic, cytotoxic, toxicological, and antifungal properties of EgEO. The oil was extracted by hydrodistillation and chemically characterized by GC/MS, revealing 39 sesquiterpenes representing 97.02 % of the total composition. Hemolytic activity was assessed via spectrophotometric quantification of hemoglobin released from human erythrocytes, while cytotoxicity was evaluated using the MTT assay in HL-60, MCF-7, and HT-29 cell lines, showing significant cytotoxicity, particularly against HL-60 (IC₅₀ = 10.8 μg/mL). Contact toxicity was tested on Tenebrio molitor larvae, pupae, and adults, with pupae being the most susceptible (LD₅₀ = 4.55 mg/mL), followed by adults and larvae. Sublethal doses (2.3 and 4.6 mg/mL) injected into larvae caused no morphological abnormalities. Antifungal activity against standard and multidrug-resistant strains of Candida glabrata was evaluated through broth microdilution, with MICs ranging from 0.11 to 3.69 mg/mL and MFCs from 0.92 to 3.69 mg/mL. Time-kill assays indicated that EgEO at MIC had fungistatic activity, while at 2 × MIC it was fungicidal. In vivo efficacy, assessed using T. molitor as an infection model, demonstrated that EgEO at a sublethal dose (2.302 mg/mL) was effective against the standard C. glabrata strain. Overall, EgEO showed low hemolytic activity, significant antitumor effects, and notable antifungal efficacy, with low toxicity in vivo, particularly at sublethal concentrations. These results support the therapeutic potential of E. gracillima essential oil as a natural agent with antifungal and anticancer properties.
Amide alkaloids from the fruits of Piper longum L. and their bioactivities
Eight previously undescribed amide alkaloids [1-5], including three pairs of enantiomers [(±)-3, (±)-4, and (±)-5], along with 17 known compounds (6-22), were isolated from the fruits of Piper longum L with chromatographic techniques and chiral separation. The planar structures and relative configurations of these compounds were elucidated using HR-ESI-MS and NMR analyses, while the absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-22 were assessed for their in vitro NO inhibition, cytotoxic, and anti-diabetic activities. Compounds (+)-5, 7, and 8 showed moderate NO inhibitory activity (10 μM < IC < 30 μM). Compounds 1, 9, and 13 exhibited significant cytotoxic effects against HeLa cells, with IC values of 9.99 ± 0.62, 6.25 ± 0.32, and 9.61 ± 0.48 μM, respectively. Compounds (+)-4, 7, 8, 9, 11, 12, 13, 15, and 16 showed potent cytotoxicity against HT-29 cells with IC values ranging from 2.65 to 7.78 μM. Compounds (+)-4, 6, and 16 exhibited weak cytotoxicity against MCF-7 cells (IC > 30 μM). Additionally, compound 6 showed moderate inhibitory activity against α-glucosidase with an IC of 112.03 ± 3.69 μM, whereas compound 8 significantly inhibited PTP1B, with an IC of 9.06 ± 0.68 μM. These findings offer valuable insights into the potential application of amide alkaloids from P. longum in developing functional foods and pharmaceuticals, highlighting their promise in health promotion.
