[Research progress in preparations of Panax ginseng].

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.

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 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.

Xylopsides A-D, four rare guaiane dimers with two unique bridged pentacyclic skeletons from Xylopia vielana.

Four unprecedented guaiane dimers, xylopsides A-D (1-4), were isolated and identified from the roots of Xylopia vielana. The structures of 1-4 were elucidated by spectroscopic analysis, Cu Kα X-ray crystallography and CD spectra. 1-4 showed two bridged pentacyclic skeletons between two guaiane-type sesquiterpenes, which were characterized as two different bridged ring systems. Among these compounds, 4 exhibited a moderate inhibitory activity against the production of nitric oxide with an IC50 value of 25.7 µM in RAW264.7 cells stimulated by LPS.

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.

Cytotoxic pentacyclic triterpenoids from Prinsepia utilis.

Phytochemical investigation of the aerial parts of Prinsepia utilis Royle resulted in the isolation and identification of ten pentacyclic triterpenoids, including two new triterpenoids, 2α-O-trans-p-coumaroyl-3ß,19α-dihydroxy-urs-12-en-28-oic acid (1) and 2α-O-cis-p-coumaroyl-3ß,19α-dihydroxy-urs-12-en-28-oic acid (2), along with eight known pentacyclic triterpenoids (3-10). The structures were elucidated by extensive spectroscopic methods and by comparison to previously reported spectroscopic data. Most of these compounds showed significant cytotoxic activities against four human cancer cell lines (A549, HCT116, MDA-MB-231, and CCRF-CEM), and the structure-activity relationships are also discussed.

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.

Sesquiterpene lactones from Inula hookeri.

Four new sesquiterpene lactones, (1 S,5 R,6 S,7 S,8 R,9 R,10 S,11 S)-6-acetoxy-9-hydroxy-4-oxo-pseudoguai-2(3)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-ethoxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-hydroxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, and 14-acetoxy-1 ß,5 α,7 αH-4 ß-hydroxy-guai-9(10),11(13)-dien-12,8 α-olide, along with 26 known sesquiterpene lactones, were isolated from the whole plants of Inula hookeri C. B. Clarke. Their structures were established based on spectroscopic methods including HRESIMS, 1D and 2D NMR, and CD techniques. All compounds were evaluated for their cytotoxic activities against HepG2, HeLa, PC-3, and MGC-803 cell lines by CCK-8 assay. Some of the isolates, especiallly pseudoguaianolides and guaianolides, exhibited significant cytotoxicities against these four examined cell lines.

Three new guaiane-type sesquiterpenoids and a monoterpenoid from Litsea lancilimba Merr.

Three undescribed guaiane-type sesquiterpenes (1-3), and a monoterpenoid (4) along with eleven known compounds (5 - 15) were isolated from the crude extract of Litsea lancilimba Merr. The structures of all the isolated compounds were extensively elucidated on the basis of comprehensive spectroscopic techniques (HRESIMS, 1 D NMR, and 2 D NMR). Their relative and absolute configurations were comprehensively established by NOESY spectroscopy, circular dichroism (ECD) and the calculated ECD analysis. All the isolates were tested for anti-inflammatory activity by measuring the amount of nitric oxide production. Amongst tested compounds, compounds 1 - 3 exhibited moderate inhibitory activities against the production of nitric oxide with IC50 value of 35.5, 32.1, 46.7 µM in RAW264.7 cells stimulated by LPS, respectively.

Metals-triggered compound CDPDP exhibits anti-arthritic behavior by downregulating the inflammatory cytokines, and modulating the oxidative storm in mice models with extensive ADMET, docking and simulation studies.

Triggering through abiotic stress, including chemical triggers like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metal Nickel on actinobacteria Streptomyces sp. SH-1327 to obtain a stress-derived compound was firstly investigated. A new compound cyclo-(D)-Pro-(D)-Phe (CDPDP) was triggered from the actinobacteria strain SH-1327 with the addition of nickel ions 1 mM. The stress compound was further evaluated for its anti-oxidant, analgesic, and anti-inflammatory activity against rheumatoid arthritis through in-vitro and in-vivo assays in albino mice. A remarkable in-vitro anti-oxidant potential of CDPDP was recorded with the IC50 value of 30.06 ± 5.11 µg/ml in DPPH, IC50 of 18.98 ± 2.91 against NO free radicals, the IC50 value of 27.15 ± 3.12 against scavenging ability and IC50 value of 28.40 ± 3.14 µg/ml for iron chelation capacity. Downregulation of pro-inflammatory mediators (NO and MDA), suppressed levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-Iß) and upregulation of expressions of anti-oxidant enzymes (GSH, catalase, and GST) unveiled its anti-inflammatory potential. CDPDP was analyzed in human chondrocyte cell line CHON-001 and the results demonstrated that CDPDP significantly increased cell survival, and inhibited apoptosis of IL-1ß treated chondrocytes and IL-1ß induced matrix degrading markers. In addition, to evaluate the mitochondrial fitness of CHON-001 cells, CDPDP significantly upregulated pgc1-α, the master regulator of mitochondrial biogenesis, indicating that CDPDP provides protective effects in CHON-001 cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of the CDPDP showed that CDPDP is safe in cases of hepatotoxicity, cardiotoxicity, and cytochrome inhibition. Furthermore, docking results showed good binding of CDPDP with IL-6-17.4 kcal/mol, and the simulation studies proved the stability between ligand and protein. Therefore, the findings of the current study prospect CDPDP as a potent anti-oxidant and a plausible anti-arthritic agent with a strong pharmacokinetic and pharmacological profile.

Guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li: And their anti-inflammatory activities.

The phytochemical assessment of Cinnamomum migao H. W. Li fruits illustrated the isolation and identification of ten undescribed guaiane-type sesquiterpenoids "miganoids A-J″ and one undescribed sesquiterpene "7(S)-(hydroxypropanyl)-3-methyl-2-(4-oxopentyl) cyclohex-2-en-1-one". The extensive analysis of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD) analysis entirely corroborated the configuration and confirmation of these isolated compounds. Moreover, the anti-inflammatory properties of the reported compounds were established by determining the LPS induced nitric oxide production. In the current study, miganoid C is testified the most active compound with about 89% NO inhibition. Additionally, miganoids C, E, and G also exhibited moderate inhibitory effects against the pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). The IC50 values for miganoid C and miganoid G were determined as 19.4 and 14.5 µΜ against TNF-α mRNA, respectively.

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.

A metabonomic approach to chemosensitivity prediction of cisplatin plus 5-fluorouracil in a human xenograft model of gastric cancer.

The prediction of chemosensitivity is a challenging problem in the management of cancer. In the present study, a metabonomic approach was proposed to assess the feasibility of chemosensitivity prediction in a human xenograft model of gastric cancer. BALB/c-nu/nu mice were transplanted with MKN-45 cell line to establish the xenograft model. The mice were then randomized into treatment group (cisplatin and 5-fluorouracil) and control group (0.9% sodium chloride), and their plasma were collected before treatment. Metabolic profiles of all plasma samples were acquired by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (HPLC/Q-TOF-MS). Based on the data of metabolic profiles and k-Nearest Neighbor algorithm, a prediction model for chemosensitivity was developed and an average accuracy of 90.4% was achieved. In addition, a series of endogenous metabolites, including 1-acyl-lysophosphatidycholines, polyunsaturated fatty acids and their derivatives, were determined as potential indicators of chemosensitivity. In conclusion, our results suggest that the proposed metabonomic approach allows effective chemosensitivity prediction in human xenograft model of gastric cancer. The approach presents a new concept in the chemosensitivtiy prediction of cancer and is expected to be developed as a powerful tool in the personalized cancer therapy.

Japonicones E-L, dimeric sesquiterpene lactones from Inula japonica Thunb.

Eight new dimeric sesquiterpene lactones (japonicones E-L, 1- 8), including a novel sesquiterpene dimer bearing a rare hydroperoxide group (japonicone E, 1), were isolated from the aerial part of Inula japonica Thunb. Their structures were determined mainly by the use of 1D and 2D NMR spectroscopic techniques including HSQC, (1)H-(1)H COSY, HMBC, and NOESY. All the isolates were tested for inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among the compounds tested, japonicone F (2) showed the strongest activity with the IC(50) value of 4.1 microg/mL.

Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum.

Ten steroidal alkaloids - cyclopamine, veratramine, jervine, 3, 15-diangyloylgermine, 3-angyloylzygadenine, 3-veratroyl zygadenine, 15-veratroylgermine, germine, veratrosine and pseudojervine - from Veratrum dahuricum, together with the ethanol extract and total alkaloids, were evaluated for their antitumor and antiplatelet activities. Cyclopamine, veratramine and germine significantly inhibited the hedgehog pathway in NIH/3T3 cells. Cyclopamine exerted a potent inhibitory effect against the growth of PANC-1 tumors in mice, with inhibition rates of 40.64%, 44.37%, 46.77% at doses of 5.0, 15.0 and 50.0 mg kg-1, respectively. Veratroylgermine was found to produce the strongest inhibition against the platelet aggregation induced by arachidonic acid, with inhibition rate of 92.0% at 100 microM.

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.

A metabonomic approach to early prognostic evaluation of experimental sepsis by (1)H NMR and pattern recognition.

This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis.

Japonicones A-D, bioactive dimeric sesquiterpenes from Inula japonica Thunb.

Four new dimeric sesquiterpene lactones japonicones A-D (1-4), comprised by eudesmane and guaiane sesquiterpenes, were isolated from the aerial part of Inula japonica Thunb. The structures and stereochemistry of 1-4 were elucidated by use of 2D NMR spectroscopic techniques, X-ray crystallography and modified Mosher method. Japonicone A (1) showed the most potent cytotoxicities against four tumor cell lines, A549, LOVO, CEM and MDA-MB-435.

A new triterpenoid from Brucea javanica.

A new triterpenoid, bruceajavanin C (1), together with bruceosides A and B (2 and 3), bruceines D and E (4 and 5), yadanziosides A and G (6 and 7), (20R)-O-(3)-alpha-L-arabinopyranosylpregn-5-ene-3beta,20-diol (8), and alpha-D-glucopyranoside, (3beta, 20R)-3-hydroxypregn-5-en-20-yl (9) were isolated from the aerial parts of Brucea javanica. The structure of 1 was elucidated on the basis of 2D-NMR spectroscopic analysis. In addition, compounds 1, 3, 4, 5, and 6 exhibited mild inhibitory effect on NO production in LPS-stimulated RAW264.7 cells.

Xylopidimers A-E, Five New Guaiane Dimers with Various Carbon Skeletons from the Roots of Xylopia vielana.

Five new guaiane dimers, xylopidimers A-E (1-5), were isolated and identified from the roots of Xylopia vielana. The structures of 1-5 were elucidated by spectroscopic analysis and further confirmed by single-crystal X-ray diffraction. On the basis of the results of single-crystal X-ray analysis, 1-5 showed different carbon skeletons. Among these compounds, the unique connecting patterns of 1 and 2 caused significant differences on their carbon skeletons, which have not been reported. Moreover, 3-5 were also three new guaiane dimers. Among these compounds, 4 exhibited potent inhibitory activity against the production of nitric oxide with an IC50 value of 4.59 µM in RAW264.7 cells stimulated by lipopolysaccharide.