[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.

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.

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).

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.

Three new sesquiterpene lactones from Inula britannica.

One new 1,10-secoeudesmanolide (1), two eudesmanolides (2 and 3), together with nine known compounds (4-12) were isolated from the aerial parts of Inula britannica. The structures of the new compounds were elucidated by detailed spectroscopic analysis, including HRESIMS and 2D-NMR spectroscopic method. In addition, compounds 1-4 were tested for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages.

New sesquiterpenic acids from Inula wissmanniana.

Eight new (1-8) and two known (9 and 10) sesquiterpenic acids featuring α-methylene-γ-carboxyl units were isolated from the whole plants of Inula wissmanniana, along with two new germacranolides (11 and 12). Their structures were elucidated based on detailed spectroscopic analysis, including HRESIMS, 1D and 2D NMR, and X-ray crystallography. Notably, the skeleton of 1 was firstly discovered from nature, while that of 2 was discovered for the second time. All the compounds were evaluated for their inhibition against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages. Compound 11 exhibited the strongest activity with the IC50 value of 1.04 µM.

Bioactive eudesmane and germacrane derivatives from Inula wissmanniana Hand.-Mazz.

Phytochemical investigation of Inula wissmanniana Hand.-Mazz. afforded 21 eudesmane and germacrane derivatives, including rare 4,5-secoeudesman-12,5-olide, eudesman-12,5-olide, 3,4-secoeudesman-12-oic acid, and germacra-4-en-12,6-olides. Their structures were elucidated by combinative analyses of MS, NMR, electronic circular dichroism, and X-ray crystallography data. Moreover, most of the isolates exhibited inhibition against lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages and cytotoxicity in HepG2, PC-3, and MGC-803 tumor cells.

Five new sesquiterpene lactones from Inula hupehensis.

Four new pseudoguaianolides (1-4), one new guaianolide (5), together with ten known compounds (6-15) were isolated from the aerial parts of Inula hupehensis. Their structures were elucidated mainly on the basis of 1D and 2D spectroscopic methods and circular dichroism analysis. In addition, compounds 1-10 and 13 were tested for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Compounds 2, 6, 8 and 9 exhibited significant inhibitory activities with IC50 values in the range of 0.6-6.6 µM.

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.

Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia.

Aphanamgrandiol A (1), a novel triterpenoid with a bicyclo[3,2,1]octane ring skeleton produced by 2,3-ring opening and 2,6-ring closure, was isolated from the stems of Aphanamixis grandifolia. The structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and determined unambiguously by X-ray crystal diffraction. Aphanamgrandiol A showed moderate cytotoxicities against MCG-803, SKOV-3, HCT116 and HepG2 cell lines.

Phenylpropanoids and lignanoids from Euonymus acanthocarpus.

A new phenylpropanoid derivative (1), along with five phenylpropanoids (2-6), two monoepoxy lignans (8-9), one bisepoxy lignan (10), two cyclolignans (11-12), six neolignans (7, 13-17), two mixed lignan-neolignans (18-19), two lignan glycosides (20-21), and four flavonolignans (22-25), were isolated from the stems and twigs of Euonymus acanthocarpus. Compounds 2-3, 6-8, 12, and 14-25 were obtained from Celastraceae family for the first time, and compounds 5 and 9 were isolated from Euonymus genus for the first time. All the compounds were tested for cytotoxicity against SK-OV-3 and MCG-803 human tumor cell lines. Compounds 3, 10, 12, and 18 showed weak cytotoxicity against SK-OV-3 cell line, and compounds 3-4, 10-13, and 19 showed weak cytotoxicity against MCG-803 cell line.

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.

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.

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.

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.

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.

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.

Biflavonoids from Daphne feddei and their inhibitory activities against nitric oxide production.

Bioassay-directed fractionation led to the isolation of two new biflavonoids and 13 known biflavonoids from a sample of the dried stem barks of Daphne feddei. The structures of compounds 1 and 2 were elucidated as 2''-methoxy-daphnodorin C (1) and 2''-methoxy-2-epi-daphnodorin C (2) on the basis of detailed spectroscopic analysis and X-ray crystallography. All 15 biflavonoids were tested for inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 1, 2, 8, 10, 14 and 15 showed varying degrees of inhibitory activities against the production of NO in tested concentration of 25, 50, 75 and 100 microg/ml.