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Background: Streptococcus mutans is a well-known oral pathogen that plays a critical role in the development of dental caries. Many studies have been directed to discover the chemical compounds present in natural products to inhibit the growth and biofilm formation activity of S. mutans. Thymus essential oils exhibit good inhibition on the growth and pathogenesis of S. mutans. However, details about the active compounds in Thymus essential oil and the inhibition mechanism still remain unclear. The aim of this study was to investigate the antimicrobial activity of 6 Thymus species (Three samples of Thymus vulgaris, two samples of Thymus zygis, and one sample of Thymus satureioides essential oils) on S. mutans, to identify the potential active components, and to reveal the underlying mechanism. Methods: The composition of Thymus essential oils was analyzed by gas chromatography-mass spectrometry. And its antibacterial effect was evaluated based on the bacterial growth, acid production, biofilm formation and genetic expression of virulence factors by S. mutans. Potential active components of the Thymus essential oil were identified using molecular docking and correlation analysis. Results: GC–MS analysis showed that the major components in the 6 Spain Thymus essential oils were linalool, α-terpineol, p-cymene, thymol and carvacrol. MIC and MBC analysis showed that 3 Thymus essential oils showed very sensitive antimicrobial activity, and were chosen for further analysis. The 3 Thymus essential oil exhibited a significant inhibitory effect on acid production, adherence and biofilm formation of S. mutans and the expression of virulence genes, such as brpA, gbpB, gtfB, gtfC, gtfD, vicR, spaP and relA. Correlation analysis showed that phenolic components, such as carvacrol and thymol, were positively related to DIZ value, which suggests that they are the potential antimicrobial components. Molecular docking between the Thymus essential oil components and virulence proteins also found that carvacrol and thymol exhibited strong binding affinity with functional domains of virulence genes. Conclusions: Thymus essential oil showed significant inhibition against the growth and pathogenesis of S. mutans depending on their composition and concentration. And phenolic compounds, such as carvacrol and thymol, are the major active components. Thymus essential oil could be used in oral healthcare products as a potential anti-caries ingredient. [ABSTRACT FROM AUTHOR]

A total of six new alkaloids, melodinhenines A–F ( 1 – 6 ), were isolated from Melodinus henryi . Melodinhenines A and B are new eburnan–vindolinine-type bisindole alkaloids and melodinhenines C–F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan–vindolinine-type bisindole alkaloid using this method. [ABSTRACT FROM AUTHOR]

Abstract: A phytochemical study on the ethanolic extract of the stem barks of Uncaria laevigata leads to the isolation and characterization of 18 triterpenoid compounds. Ten of these are new, including one novel heptanortriterpenoid (1), four ursane triterpenes (2–4, 10), and five oleanane triterpenes (5–9). Their structures were established by spectroscopic methods, especially by 2D-NMR and MS analyses. All these isolates were evaluated for their inhibitory effects on α-glucosidase: ursolic acid and 3 showed potent activities with IC50 values of 16±2.2 and 49±3.7μM, respectively. [Copyright &y& Elsevier]

Abstract: Two new sesqui-neolignans with novel conjugation way, simonol A (1), featuring a unique motif of a 5,5-dihydro-pyran with a hemiketal carbon, while simonol B (2) possessing two dihydronfuran rings in the same direction, were isolated from the ethanol extract of the fruits of Illicium simonii. Their structures were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and calculation of electronic circular dichroism (ECD) using density functional theory (DFT). The two isolates were evaluated for their inhibitory activities against the growth of four lines of human cancer cells (NCI-H460, SMMC-7721, MCF-7, BGC-823): 1 showed strong activities comparable to 5-Fluorouracil, and 2 to a less content. In addition, plausible biosynthetic routes for the two compounds were also proposed. [Copyright &y& Elsevier]

Abstract: Two novel dimeric indole alkaloids were isolated from the leaves and twigs of Psychotria henryi. Their structures were established by chemical and spectroscopic methods. Compound 1 was a novel dimeric tryptamine-related alkaloid that contained an unprecedented decacyclic ring system, and compound 2 featured a pyrido[3,4-b]indole moiety adjacent to a pyrrolidinoindole skeleton. The absolute configurations of compounds 1 and 2 were determined by calculation of electronic circular dichroism (ECD) using density functional theory (DFT). [Copyright &y& Elsevier]

Abstract: Four new sesquiterpenes, chlorajapolides F–I (1–4), along with nine known terpenoids (5–13) were isolated from the aerial part of Chloranthus japonicus. Their structures were elucidated on the basis of spectroscopic analysis, and a lindenane sesquiterpene, named 9-hydroxy-heterogorgiolide, previously isolated from the C. japonicus, was revised as its 8-epimer (1a). Moreover, methanol extract (ME), EtOAc fraction (EF), water fraction (WF), and all isolates (1a, 1–13) were evaluated for their cytotoxicities using two human cancer cell lines. [Copyright &y& Elsevier]

Abstract: From the flowers of Chrysanthemum indicum, three new germacrane-type sesquiterpene stereoisomers (1β,3α,5β-trihydroxyl-7-isopropenyl-germacren-4(15), 10(14)-diene (1), 1β,3β,5α-trihydroxyl-7-isopropenyl-germacren-4(15), 10(14)-diene (2), 1β,3β,5β-trihydroxyl-7-isopropenyl-germacren-4(15), 10(14)-diene (3)) were isolated, whose structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of compound 1 was determined by a single crystal X-ray diffraction study using a mirror Cu Kα radiation. [Copyright &y& Elsevier]

A novel lindenane sesquiterpene with an unprecedented 18-membered triester ring, named chlorafortulide (1), along with one known lindenane sesquiterpene (2) and nine known lindenane sesquiterpene dimers (3–11), was isolated from the whole plant of Chloranthus fortunei. Their structures and relative configurations were elucidated on the basis of spectroscopic analysis. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Henriol D (4), shizukaols E (8), G (9), M (10), and O (11) showed significant anti-inflammatory activities with IC50 values of 1.90, 3.68, 1.95, 7.01, and 1.95 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du decoction (HLJDD) (Oren-gedoku-to in Japanese) as a famous traditional Chinese recipe is composed of Rhizoma coptidis, Radix scutellariae, Cortex phellodendri and Fructus gardeniae. It has been used to treat inflammation for nearly two thousand years. Aim of the study: To explore the material base for the anti-inflammatory activity of formula HLJDD, its extract was fractionated on D101 macroporous resin to afford two fractions, HLJDD-1 and HLJDD-2. The whole formula, HLJDD-1 and HLJDD-2, and four typical component compounds were then evaluated for their effects on inflammation-related parameters using lipopolysaccharide (LPS)-induced RAW264.7 cells as a model system. Materials and methods: The effect of HLJDD on carrageenan-induced mice paw edema was first evaluated. A series of inflammation-related parameters including malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were then measured in LPS-induced RAW264.7 cells treated with HLJDD, its two fractions, and four typical component compounds (geniposide, baicalin, berberine and baicalein). Results: With the help of principal component analysis (PCA) technique, the data obtained revealed that the two fractions and the major group of compounds in HLJDD (iridoids, flavonoids and alkaloids) complement each other with particular emphasis to synergistically exert anti-inflammatory effects. Conclusions: This study demonstrated that HLJDD exhibited anti-inflammatory effect as a “whole”, which justified the combined use of the four component herbs forming the compound prescription and suggested quality control of HLJDD based on its three types of components. [Copyright &y& Elsevier]

Abstract: Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, is clinically used for the treatment of vascular dementia (VD). This study compared the pharmacokinetics of paeoniflorin, the main active ingredients in Paeonia lactiflora Pall, in VD and normal rats administrated with DSS or pure paeoniflorin. The absorptions of paeoniflorin in both VD and normal group of rats were better when orally administrated with DSS than that with pure paeoniflorin, which justified the combined use as formula DSS. Moreover, a better absorption of paeoniflorin in rats of the VD than in normal group was observed, which is helpful for the treatment of VD. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Glycyrrhizae uralenis (GU) is often prescribed together with Cortex daphnes (CD) in traditional Chinese medicinal practice to increase the efficacy of CD on the treatment of rheumatoid arthritis (RA), but the reasons were still unknown. In order to clarify the rationality of herbaceous compatibility between CD and GU, the comparative evaluations on pharmacokinetic behaviors of daphnetin (a predominantly active ingredient in CD) after intragastric administration of CD and CD–GU (combination of CD and GU) extract were studied. In addition, the effects of glycyrrhizin and liquiritin, active ingredients of Glycyrrhiza triterpenes and Glycyrrhiza flavones respectively, on the pharmacokinetics of daphnetin were also investigated. Materials and methods: Five groups of rats were orally administered with CD extract, CD–GU extract, pure daphnetin, co-administration of daphnetin and glycyrrhizin as well as co-administration of daphnetin and liquiritin at the same single dose of daphnetin (20mg/kg). The rat plasma concentrations of daphnetin were determined by our developed UPLC–MS/MS method. The pharmacokinetics of daphnetin in above groups were investigated and compared. Results: Comparing with oral administration of CD extract, AUC and T max of daphnetin significantly increased after giving CD–GU (p<0.05). In addition, in comparison to daphnetin alone, co-administration of daphnetin with liquiritin significantly increased the AUC and C max of daphnetin for ~1.5-fold, while co-administered with glycyrrhizin showed limited impact on the pharmacokinetics of daphnetin. Conclusions: In this study, it was found that liquiritin, one of the major components of GU, significantly enhanced the bioavailability of the main component daphnetin in CD. In addition, the bioavailability of daphnetin in the CD–GU prescription was also significantly higher than that in CD alone, which could be due to liquiritin. Such results explained the mechanism of the increased efficacy in treating RA with the combined use of CD and GU. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy. Aim of the study: In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi−Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi−Ganjiang aqueous extract was carried out. Materials and methods: A sensitive, specific and rapid LC−MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi−Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0). Results: Comparing with Fuzi group, both T 1/2 and AUC0−t of AC and HA decreased (P<0.05), while T 1/2, AUC0−t and C max of BAC, BHA increased (P<0.05) in Fuzi−Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA. Conclusion: The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi−Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi−Ganjiang to decrease toxicity and increase efficacy. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The root of Peucedanum praeruptorum Dunn (PPD) is a commonly used traditional Chinese medicine for the treatment of asthma. Its major constituents, coumarins, were presumed to be responsible for its efficacy. Aim of the study: The potential of coumarins from PPD (CPPD) as anti-asthma agent was investigated. Materials and methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic airway inflammation. CPPD was administered intragastrically before every OVA challenge. Airway reactivity to the intravenous administration of acetylcholine chloride was measured 48h after final OVA inhalation. Airway inflammation was evaluated by leukocyte counts of bronchoalveolar lavage fluid (BALF) and histopathological analysis of lung lesions. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13 and IFN-γ in BALF and OVA-specific immunoglobulin (Ig) E in serum, and activity of eosinophil peroxidase (EPO) in lung was measured. The percentage of CD4+CD25+Foxp3+ regulatory T cells among CD4+ T cells in spleen was analyzed by flow cytometry. Results: Compared with model group, CPPD significantly reduced airway hyperreactivity and airway eosinophilic inflammation, improved pathologic lesion of the lungs, reduced levels of IL-4, IL-5, IL-13 in BALF and OVA-specific IgE in serum, inhibited the activities of EPO in lung, and up-regulated levels of IL-10 and IFN-γ in BALF as well as the percentage of CD4+CD25+Foxp3+ regulatory T cells in spleen. Conclusion: CPPD can significantly suppress OVA-induced airway inflammation, airway hyperreactivity and Th2 predominant response in mice, showing great therapeutic potential for the treatment of allergic asthma. [Copyright &y& Elsevier]

Abstract: Salviae miltiorrhizae is one of the most commonly used herbal plants in the treatment of numerous ailments including cardiovascular diseases for hundreds of years. According to the theory of traditional Chinese herbal medicine, S. miltiorrhizae is always used in combination with borneol to obtain better pharmacological effects. The purpose of this study was to investigate the effects of borneol on the pharmacokinetic and bioavailability of S. miltiorrhizae. The pharmacokinetics studying on rosmarinic acid, salvianolic acid A and salvianolic acid B which are the main active compounds of S. miltiorrhizae in rat plasma, was achieved using a optimal high-performance liquid chromatographic technique coupled with liquid–liquid extraction method. After administration of either single salvianolic acids or salvianolic acids in combination with borneol, plasma concentrations of rosmarinic acid, salvianolic acid A and salvianolic acid B of male Sprague–Dawley rats were determined at different time points (5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360min). In comparison with salvianolic acid extract alone, there were statistically significant differences in pharmacokinetic parameters of rosmarinic acid, salvianolic acid B and salvianolic acid A, and the bioavailability of the three salvianolic acids increased by different degrees when the salvianolic acid extract and borneol were administered together. These results indicated that borneol could enhance the intestinal absorption, decrease the distribution and inhibit the metabolism of salvianolic acids. [Copyright &y& Elsevier]

Abstract Ethnopharmacological relevance Polygonum multiflorum Thund., a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating hypertension, hyperlipidemia, premature graying of hair, and etc., has aroused wide concern for its reported potential liver toxicity. Due to its various active ingredients, the mechanisms underlying the hepatotoxicity of raw Polygonum multiflorum Thund (RPM) remain largely unknown. Aim of the study 1H NMR metabolomics was used to study the mechanism of RPM induced hepatotoxicity and disclosed the existence of hepatotoxicity and hepatoprotection conversion during RPM administration in mice. Materials and Methods Three dosages of RPM were administered by gavage to mice for consecutive 28 days. The serum and liver samples were collected and then subjected for histopathology observation, biochemical measurement and 1H NMR metabolic profiling. Results RPM caused oxidative stress and mitochondria dysfunction in mice, resulting in significant disturbance in energy metabolism, amino acid metabolism and pyrimidine metabolism and also inducing inflammatory responses. RPM induced hepatotoxicity in an apparent non-linear manner: the most severe in low dosage group, and to a less extent in medium group according to metabolomics analysis. The attenuation of liver injury in mice livers might result from the therapeutic effects, such as anti-oxidative capacity of RPM components. Conclusion RPM exerted a complicated non-linear manner in healthy recipients, switching between hepatoxicity and hepatoprotection dependent on the dosage and status of the body. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. Aim of the study Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl 4 -induced liver injury in rats and to explore the underlying mechanisms. Materials and methods Hepatic fibrosis was induced by intraperitoneal injection of CCl 4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. Results HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. Conclusion This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract: Two new compounds, a neolignan (1), and a benzofuran derivative (2), along with 6 known compounds (3–8), were isolated from the aerial parts of Leontopodium leontopodioides. The structures of the new compounds were elucidated as (7R,8S)-3,5′-dimethoxy-4′,7-epoxy-8,3′-neolignane-5,9,9′-triol (1) and (2R)-12-hydoxy-4-methoxy-tremeton (2) on the basis of their spectroscopic data, respectively. All of the isolates were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages and compounds 1 and 8 exhibited inhibitory activity with IC50 values of 35.80 and 24.41μM, respectively. [Copyright &y& Elsevier]

A novel aporphine alkaloid, magnofficine (1), has been isolated from the root barks of the Chinese medicinal plant Magnolia officinalis, along with seven known compounds. Elucidations of their structures were achieved by spectroscopic methods. Magnofficine is the first example of an adduct of aporphine alkaloid and 4-hydroxyphenethylamino bridged by a methylene. [Copyright &y& Elsevier]

Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means. Image 1 [ABSTRACT FROM AUTHOR]