An extensive pharmacological evaluation of novel anti-nociceptive and IL-6 targeted anti-inflammatory guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li through in-depth in-vitro, ADMET, and molecular docking studies.

Guaiane-type sesquiterpenoids are most prevalent in the genus Cinnamomum. Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated from Cinnamomum migao. The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids 1 and 2 exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC50 values were determined as 9.52 and 13.42 µΜ against IL-6 mRNA, respectively. Similarly, subcutaneous injection of n-BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids 1 and 2 displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene 2 which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids from C. migao will provide new evidence for the traditional use of this species to treat inflammation and nociception.

Cross-talk between the RAS-ERK and mTOR signalings-associated autophagy contributes to tripterygium glycosides tablet-induced liver injury.

BACKGROUND AND AIMS: Drug-induced liver injury (DILI) remains a critical issue and a hindrance to clinical application of Tripterygium Glycosides Tablet (TGT) despite its favorable therapeutic efficacy in rheumatoid arthritis. Herein, we aimed to elucidate the molecular mechanisms underlying TGT-induced hepatotoxicity. METHODS: Chemical profiling of TGT was identified by UPLC-Q/TOF-MS/MS and its putative targets were predicted based on chemical structure similarity calculation. Following "DILI-related gene-TGT putative target" interaction network construction, a list of key network targets was screened according to nodes' topological importance and functional relevance. Both in vivo and in vitro experiments were performed to determine drug hepatotoxicity and the underlying mechanisms. RESULT: A total of 49 chemical components and 914 putative targets of TGTs were identified. Network calculation and functional modularization screened RAS-ERK and mTOR signalings-associated autophagy to be one of the candidate targets of TGT-induced hepatotoxicity. Experimentally, TGT significantly activated RAS-ERK axis, elevated the number of autophagosomes and the expression of LC3II protein, but reduced the expression of p62 protein and suppressed mTOR phosphorylation in the liver tissues of TGT-induced acute liver injury mice and chronic liver injury mice in vivo and AML12 cells in vitro. Moreover, TGT and mL-098 (an activator of RAS) co-treatment reduced AML12 cell viability via regulating autophagy and TGT-induced liver injury-related indicators more dramatically than TGT treatment alone, whereas Salirasib (an inhibitor of RAS) had an opposite effect. CONCLUSION: RAS-ERK-mTOR cross-talk may play a crucial role in TGT-induced hepatocyte autophagy, offering a promising target for developing novel therapeutics to combat TGT-induced hepatotoxicity.

Emerging Biopharmaceuticals from Pimpinella Genus.

Evolved over eons to encode biological assays, plants-derived natural products are still the first dawn of drugs. Most researchers have focused on natural compounds derived from commonly used Pimpinella species, such as P. anisum, P. thellungiana, P. saxifrage, and P. brachycarpa, to investigate their antioxidant, antibacterial, and anti-inflammatory properties. Ethnopharmacological studies demonstrated that the genus Pimpinella has the homology characteristics of medicine and food and mainly in the therapy of gastrointestinal dysfunction, respiratory diseases, deworming, and diuresis. The natural product investigation of Pimpinella spp. revealed numerous natural products containing phenylpropanoids, terpenoids, flavonoids, coumarins, sterols, and organic acids. These natural products have the potential to provide future drugs against crucial diseases, such as cancer, hypertension, microbial and insectile infections, and severe inflammations. It is an upcoming field of research to probe a novel and pharmaceutically clinical value on compounds from the genus Pimpinella. In this review, we attempt to summarize the present knowledge on the traditional applications, phytochemistry, and pharmacology of more than twenty-five species of the genus Pimpinella.

The Antifatigue Mechanism of Buyang-huanwu Decoction as Revealed by Serum Metabolomics in an Endurance Swimming Rat Model.

Buyang-huanwu decoction (BHD) is a classic prescription that has great potential to be developed into antifatigue functional food. It may activate blood circulation to relieve fatigue in some clinical cases by unclear mechanisms. In this study, a metabolomics approach was conducted to investigate the antifatigue mechanism of BHD. The murine fatigue model was established in rats by endurance swimming, and hemorheology, blood biochemistry, and ultraperformance liquid chromatography-mass spectrometry-based metabolomics were conducted on serum samples. The rate of weight gain, hemorheological parameters, and serum creatine kinase activities were significantly altered in model rats and they returned to a normal level after BHD administration. Pattern recognition screened 18 potential biomarkers, which are mainly involved in glycerophospholipid, arachidonic acid, and cholesterol metabolisms. The results demonstrate that the antifatigue mechanism of BHD is mainly related to the function of enhancing nerve conduction, relieving inflammation and regulating cholesterol metabolism and energy metabolism.

[A new isoflavone from Dalbergia odorifera and inhibitory activity of its tyrosinase].

Twelve flavonoids were isolated and purified from the ethyl acetate fraction of 95% ethanol extract of Dalbergia odorifera by heat reflux extraction, solvent extraction, recrystallization, normal phase silica gel, Sephadex LH-20, MCI gel and HPLC methods. The structures were identified with multiple spectroscopic methods, including 1 D-NMR, 2 D-NMR and MS. The compounds were identified as 6,7,8-trimethoxy-5,4'-dihydroxy isoflavone(1), medicarpin(2), 7,2'-dihydroxy-4'-methoxy-isoflavanol(3), biochanin A(4), prunetin(5), genistein(6), pratensein(7), 3-(4-hydroxyphenyl)-6-isopentenyl-7-methoxy-4H-chromen-4-one(8), tectorigenin(9), irisolidone(10), vestitol(11), and formononetin(12). Compound 1 was a new isoflavone, and compound 8 was isolated from D. odorifera for the first time. The results showed that compounds 1-3 had inhibitory effects on tyrosinase, with inhibition rates of 35.58%, 38.63% and 51.34% at the concentration of 1.0 mmol·L~(-1), respectively.

Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment of depression.

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).

A Novel Drug Combination of Mangiferin and Cinnamic Acid Alleviates Rheumatoid Arthritis by Inhibiting TLR4/NFκB/NLRP3 Activation-Induced Pyroptosis.

Growing evidence shows that Baihu-Guizhi decoction (BHGZD), a traditional Chinese medicine (TCM)-originated disease-modifying anti-rheumatic prescription, may exert a satisfying clinical efficacy for rheumatoid arthritis (RA) therapy. In our previous studies, we verified its immunomodulatory and anti-inflammatory activities. However, bioactive compounds (BACs) of BHGZD and the underlying mechanisms remain unclear. Herein, an integrative research strategy combining UFLC-Q-TOF-MS/MS, gene expression profiling, network calculation, pharmacokinetic profiling, surface plasmon resonance, microscale thermophoresis, and pharmacological experiments was carried out to identify the putative targets of BHGZD and underlying BACs. After that, both in vitro and in vivo experiments were performed to determine the drug effects and pharmacological mechanisms. As a result, the calculation and functional modularization based on the interaction network of the "RA-related gene-BHGZD effective gene" screened the TLR4/PI3K/AKT/NFκB/NLRP3 signaling-mediated pyroptosis to be one of the candidate effective targets of BHGZD for reversing the imbalance network of "immune-inflammation" during RA progression. In addition, both mangiferin (MG) and cinnamic acid (CA) were identified as representative BACs acting on that target, for the strong binding affinities between compounds and target proteins, good pharmacokinetic features, and similar pharmacological effects to BHGZD. Notably, both BHGZD and the two-BAC combination of MG and CA effectively alleviated the disease severity of the adjuvant-induced arthritis-modified rat model, including elevating pain thresholds, relieving joint inflammation and bone erosion via inhibiting NF-κB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream caspase-1, the reduced release of IL-1ß and IL-18, and the modulation of GSDMD-mediated pyroptosis. Consistent data were obtained based on the in vitro pyroptosis cellular models of RAW264.7 and MH7A cells induced by LPS/ATP. In conclusion, these findings offer an evidence that the MG and CA combination identified from BHGZD may interact with TLR4/PI3K/AKT/NFκB signaling to inhibit NLRP3 inflammasome activation and modulate pyroptosis, which provides the novel representative BACs and pharmacological mechanisms of BHGZD against active RA. Our data may shed new light on the mechanisms of the TCM formulas and promote the modernization development of TCM and drug discovery.

Molecular mechanism underlying the hypolipidemic effect of Shanmei Capsule based on network pharmacology and molecular docking.

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.

Phytochemical study of Ligularia subspicata and valuation of its anti-inflammatory activity.

This report illustrated isolation and identification of 42 compounds comprising five (spicatainoids A-E) undescribed eremophilanolide type sesquiterpenoids and one undescribed nor-eremophilane (spicatainoid F) from Ligularia subspicata.. Among all the isolated new compounds, 4 is reported as the first enantiomeric form of novel eremophilanolide type sesquiterpenoid. Comprehensive analysis of HRESIMS, 1D/2D NMR, experimental circular dichroism (CD), calculated ECD analysis, and X-ray crystallographic (XRD) analysis validated the complete configuration and confirmation of these isolated compounds. All the isolated compounds were tested for the anti-inflammatory potential by measuring the amount of nitric oxide production. Among the tested compounds, 4 was the most effective with 90% NO-inhibition activity. Compounds 1, 2, 3, 9, 10 18, 29, 34, 35 exhibited moderate inhibitory effects against the production of NO, while other compounds displayed no activity even at the concentration of 50 µM. Additionally, compounds 1, 3 and 4 presented moderate anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in LPS-stimulated N9 cells. The IC50 values of compounds 1, 3 and 4 were calculated 39.6 ± 2.7, 42.5 ± 3.8 and 27.60 ± 1.9 µΜ.

Network Pharmacology in Research of Chinese Medicine Formula: Methodology, Application and Prospective.

Chinese medicine (CM) is usually prescribed as CM formula to treat disease. The lack of effective research approach makes it difficult to elucidate the molecular mechanisms of CM formula owing to its complicated chemical compounds. Network pharmacology is increasingly applied in CM formula research in recent years, which is identified suitable for the study of CM formula. In this review, we summarized the methodology of network pharmacology, including network construction, network analysis and network verification. The aim of constructing a network is to achieve the interaction between the bioactive compounds and targets and the interaction between various targets, and then find out and validate the key nodes via network analysis and network verification. Besides, we reviewed the application in CM formula research, mainly including targets discovery, bioactive compounds screening, toxicity evaluation, mechanism research and quality control research. Finally, we proposed prospective in the future and limitations of network pharmacology, expecting to provide new strategy and thinking on study for CM formula.

Supplementation of Sesamin Alleviates Stress-Induced Behavioral and Psychological Disorders via Reshaping the Gut Microbiota Structure.

Sesamin, a lignan from sesame seed, has been reported to attenuate chronic mild stress-induced depressive-like behaviors. Gut microbiota play pivotal roles in mediating psychological behaviors by regulating gut barrier integrity and systemic inflammatory responses. Here, we found that oral sesamin administration (50 mg/kg·bodyweight/day) significantly attenuated depressive, aversive, repetitive, and anxiety-like behaviors in a long-term multiple nonsocial stress-treated mice model. Sesamin inhibited stress-induced gut barrier integrity damage, reduced circulating lipopolysaccharide (LPS) levels, and suppressed neuroinflammatory responses. Moreover, sesamin treatment also restructured the gut microbiome by enhancing the relative abundances of Bacteroidales and S24-7. The correlation analysis indicated that the microbiota composition changes were strongly correlated with behavioral disorders, serotonin, norepinephrine, and LPS levels. In conclusion, sesamin has preventive effects on stress-induced behavioral and psychological disorders, which might be highly related to the reshaped microbiota composition. This study provides a clue for understanding the systemic mechanism of anti-depression effects of sesamin.

Mannan Oligosaccharide Suppresses Lipid Accumulation and Appetite in Western-Diet-Induced Obese Mice Via Reshaping Gut Microbiome and Enhancing Short-Chain Fatty Acids Production.

SCOPE: Obesity is associated with gut microbiome dysbiosis. Mannose oligosaccharide (MOS) has been reported to be a potential prebiotic. The present study is aimed to determine the effects of MOS on western-diet-induced obesity and to uncover the mediating roles of the gut microbiota and microbial metabolites. METHODS AND RESULTS: Three-month-old male ICR mice are fed with a high-fat and high-fructose diet for 8 weeks. The diet-induced obese mice are then orally administrated with MOS (100 and 200 mg kg-1  d-1 ) for 4 weeks. MOS significantly reduces bodyweight gain, insulin resistance, fatty liver, and inflammatory responses in obese mice. MOS also stimulates lipolysis and inhibits lipogenesis in the adipose tissues. Moreover, MOS restructures the gut microbiome by enhancing the abundance of Bifidobacterium and Lactobacillus in obese mice. The microbial metabolite SCFAs are also increased in the feces and serum. Correlation analysis indicates that the appetite suppression and lipid-lowering effects of MOS are highly correlated with the butyrate levels. CONCLUSION: MOS suppresses the appetite, which results in less lipid deposition. The lower appetite is likely due to an altered gut microbiome and elevated SCFAs production. MOS may be a potential nutraceutical used in body weight management and gut health improvement.

Vielopsides A-E, five new guaiane-type sesquiterpenoid dimers from Xylopia vielana.

Five new guaiane-type sesquiterpenoid dimers vielopsides A-E, connecting patterns through two direct CC bonds (C-2 to C-2', C-4 to C-1'), were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOE analysis, the Cu Kα X-ray crystallographic and circular dichroism (CD) experiment. Among them, compound 5 showed moderate activity IC50 values of 33.8 µM on NO production in RAW 264.7 macrophages.

Three new alkaloids from Xylopia vielana and their antiinflammatory activities.

Three new aporphine alkaloids, xylopialoids A-C (1-3), along with three known aporphine alkioids (4-6) and three other known compounds (7-9) were isolated from the roots of Xylopia vielana. Among these three new aporphine alkaloids, xylopialoid C (3) showed a special carbamido group directly connected to the nitrogen. The chemical structures of these nine compounds were determined by a combination of 1D and 2D NMR, MS, CD spectrum and Cu Kα X-ray crystallographic analyses. All these six alkaloids were firstly tested for the inhibitory activities against the production of NO in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Among these compounds, 4 showed a potential inhibitory activity against the production of nitric oxide with IC50 value of 1.39 µM.

JNK inhibitor alleviates apoptosis of fetal neural stem cells induced by emulsified isoflurane.

Isoflurane can provide both neuroprotection and neurotoxicity in various culture models and in rodent developing brains. Emulsified Isoflurane (EI) is an emulsion formulation of isoflurane, while its underlying molecular mechanism of developemental nerve toxicity largely remains unclear. We hypothesized that EI induced fetal neural stem cells (FNSCs) apoptosis, endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK) activation. FNSCs were isolated from the cortex of SD rats during 14 days of gestation. The cell viability, cell apoptotic rates and the expression of apoptosis-related protein Caspase3, inositol requiring enzyme 1 (IRE1), poly (adenosine diphosphate-ribose) polymerase (PARP), Bax, Bcl-2, JNK, p-JNK and XBP1 were determined. Specific inhibition was performed by siRNA-targeting of JNK in FNSCs. EI could increase the p-JNK, JNK and caspase3 protein expression, the JNK pathway was activated by EI, and EI-induced apoptosis was blocked by inhibiting JNK pathway with SP600125 or JNK-small interfering RNA (siRNA), EI enhanced the level of IRE1, PARP, Bax/Bcl-2 and XBP1, which led FNSCs to apoptosis and ER stress. Meanwhile, dilatation of the ER lumens in FNSCs treated by EI for 24 h was significant. Green fluorescent protein (GFP) positive cell ratios were significantly decreased by FNSCs transfecting with JNK gene silencing. JNK was efficiently silenced in siRNA-JNK1 group. The results provided in-vitro evidence which supports that the underlying mechanisms of EI-induced apoptosis are the induction of ER stress and sequent JNK activation. Together, these data suggest that JNK inhibiting might be applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity. HIGHLIGHTS: 1. Prolonged treatment with high-dose EI decreased the survival level of FNSCs by inducing apoptosis and inhibiting proliferation via the JNK signaling pathway. 2. EI induced ER stress and sequent JNK activation. 3. JNK inhibiting might be applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity.

Potential neurotoxicity of prenatal exposure to sevoflurane on offspring: Metabolomics investigation on neurodevelopment and underlying mechanism.

Repeated or prolonged anesthesia to pregnant women disturbs neurodevelopment of developing infants, but its mechanism has not been elaborated absolutely. This study was conducted to investigate the mechanism of potential neurotoxicity on their offspring generation after sevoflurane anesthesia in adult animals during pregnancy based on metabolomics. 16 pregnant rats were equally assigned to sevoflurane group and control group, and serum samples were collected from their 7-day-old offspring for metabolomics analysis using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry. Principal component analysis and partial least squares-discriminate analysis were used for pattern recognition, and pathway analysis was performed by MetaboAnalyst platform. 29 metabolites were discovered as neurotoxicity related-biomarkers, among which S-Adenosylmethioninamine was inhibited dramatically after sevoflurane exposure. Prenatal exposure to sevoflurane led to a significant reduction in S-Adenosylmethionine level, as shown by enzyme-linked immunosorbent assay. Pathway analysis highlighted that prenatal exposure to sevoflurane induced alteration in arginine/proline metabolism, cysteine/methionine metabolism, and so on. The most important altered metabolic pathway was arginine/proline metabolism. This study suggests that abnormal methylation and disturbed arginine/proline metabolism may crucially contribute to the mechanism with neurotoxicity on offspring generation after sevoflurane anesthesia in adult animals during pregnancy, and dietary supplement of S-Adenosylmethionine and modulating arginine/proline metabolism may be the potential therapeutic targets for protecting neurodevelopment from detrimental effects of prenatal exposure to inhalational anesthetics.

Seven new lignan glycosides from the branches of Alangium kurzii Craib var. laxifolium.

Seven new lignan glycosides (1-3, 8-10, and 14) and 17 known compounds were isolated from the branches of Alangium kurzii Craib var. laxifolium. Their structures were established by spectroscopic analysis and circular dichroism (CD) and X-ray analysis. The isolated compounds were evaluated for their antibacterial activities against Staphylococcus aureus CI1011, Streptococcus suis CI1608, Salmonella gallinarum CI0912, Enterococcus faecalis CI1304, Aeromonas hydrophila CI1008, Escherichia coli CI151012, Vibrio parahaemolyticus CI150506, Klebsiella pneumoniae CI131216, Pseudomonas aeruginosa CI1011, Staphylococcus epidermidis CI1110, and Streptococcus agalactiae CI1302. Their minimum inhibitory concentrations (MICs) were determined by serial dilution in 96-well culture plates.

Eight new γ-lactam alkaloids from the roots of the Hemerocallis minor Mill.

Eight new γ-lactam alkaloids, hemerominors A-H (1-8), including two pair of epimers (1-4), together with six known compounds (9-14) were isolated from the roots of Hemerocallis minor Mill. The structures of 1-8 were established on the basis of extensive NMR studies and HR-MS measurements as well as comparison with literature data. The absolute configurations of 1-8 were determined by CD spectral analysis and modified Mosher's method. All of compounds were evaluated for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 13 exhibited moderate inhibitory activity against NO production and with IC50 value of 18.0 µM.

Chemical Constituents from Campylotropis hirtella.

A phytochemical investigation on the roots of Campylotropis hirtella afforded nine new isoflavones (3-9, 12, 15), two new isoflavans (10 and 11), one new coumestan (1), and three new prenylated benzoic acid derivatives (2, 13, 14), together with twenty-four known compounds. Their structures were established by spectroscopic analysis and circular dichroism data. The isolated compounds were also evaluated for their antibacterial activities against Enterococcus faecalis, Salmonella gallinarum, Streptococcus suis, Streptococcus agalactiae, Aeromonas hydrophila, Pseudomonas aeruginosa, Bacillus subtilis, Riemerella anatipestifer, and Vibrio alginolyticus.

Lignans from the Whole Plants of Hedyotis uncinella.

Two new lignans, named (7R, 8S)-balanophonin (1) and (7R, 8S)-tomentosanan A (2), together with eight known lignans, burselignan (3), (+)-isolariciresinol (4), (+)-lyoniresinol (5), 5-methoxy-(+)-isolariciresinol (6), (-)-syringaresinol (7), (+)-epipinoresinol (8), (-)-(7'S, 8S, 8'R)-4,4'-dihydroxy-3, 3', 5, 5'-. tetramethoxy-7', 9-epoxy-lignan-9'-ol-7-one (9), and (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (10) were isolated from the whole plants of Hedyotis uncinella Hook. et Am. Structures of these compounds were elucidated through 1H NMR, "C NMR, 2D NMR, ESI-MS and CD data.