Search

Hydroxysafflor yellow A (HSYA) from safflower (Carthamus tinctorius L.) possesses several medicinal properties. However, it is unknown whether HSYA is effective in the treatment of rheumatoid arthritis (RA). Hence, we investigated the effects of HSYA on the inflammation and synovial damage in rats with collagen-induced arthritis (CIA) by subjecting them to treatment with different doses of HSYA. Our results revealed that HSYA could significantly reduce paw swelling, pathological manifestations, and serum cytokine levels in rats with CIA. The HSYA-treated groups showed increased antioxidant enzyme activity in the serum and decreased expression of inflammatory mediators in the synovial tissues. Furthermore, HSYA treatment inhibited extracellular signal-regulated kinase (ERK) signalling pathway activation. Notably, the highest dose of HSYA (20 mg/kg) exhibited the best effects against RA symptoms. Therefore, our findings suggest that HSYA alleviates the inflammatory response and synovial damage in rats with CIA by inhibiting the ERK signalling pathway.

The ancient Egyptians practiced medicine with highly professional methods. They had advanced knowledge of anatomy and surgery. Also, they treated a lot of diseases including dental, gynecological, gastrointestinal, and urinary disorders. They could diagnose diabetes and cancer. The used therapeutics extended from different plants to include several animal products and minerals. Some of these plants are still used in the present day. Fortunately, they documented their life details by carving on stone, clay, or papyri. Although a lot of these records have been lost or destroyed, the surviving documents represent a huge source of knowledge in different scientific aspects including medicine. This review article is an attempt to understand some information about traditional medicine in ancient Egypt, we will look closely at some basics, sources of information of Egyptian medicine in addition to common treated diseases and therapeutics in this great civilization.

Background The present study aimed to explore the chemical characteristics of mountainous forest cultivated ginseng (MFCG) and garden ginseng (GG) with respect to their ginsenosides and oligosaccharides. Methods A high-performance liquid chromatography with diode-array detection-evaporative light-scattering detection technique was adopted to investigate the ginseosides and oligosaccharides of GG and MFCG. Results The features of ginsenosides showed Rg1/Re in different parts of GG and MFCG: main root > lateral root > fibrous root, as well as Rg1/Re in the main root: MFCG > GG, indicating that the Rg1/Re is related to age of the ginseng. In most cases, Rg1/Re 1 in entire MFCG. In addition, the ratio of protopanaxadiol/protopanaxatriol in main root of GG is approximately 1 and, in the main roots of MFCG, the ratio is approximately 2 and, furthermore, Ro/Rb1 of MFCG is lower than that of GG. Analysis of oligosaccharides showed that GG mainly contained sucrose and MFCG mainly contained sucrose and maltose, and the ratio of sucrose to maltose was at least more than 4:1 in GG and less than 4:1 in MFCG in most cases, indicating the characteristics of oligosaccharides of MFCG are primarily affected by its growing environment. The results also showed that ginsenoside Re is most probably the biosynthetic precursor of ginsenoside Rg1 (i.e. Re was synthesized first and then transformed to Rg1 in vivo). Conclusion The characteristics of Rg1/Re and higher maltose can be regarded as one of the characteristics of high quality MFCG, and these characteristics are related to a higher age and the cultivation environment of ginseng. The formation mechanism of these characteristics for GG and MFGG is also discussed. As far as we know, the present study is the first to determine the difference of Rg1/Re and oligosaccharides between MFCG and GG and this provides a reference for the quality control criterion of GG and MFCG. © 2020 Society of Chemical Industry.

Objective The research indicated that the nature of Chinese medicine is mainly related to body's substance and energy metabolism. The purpose of the study is to elucidate the substance basis for warm nature of Poria cocos (called Fuling (FL) in Chinese). Methods In terms of the effects of its separated fractions on the substance and energy metabolism in rat models of cold-deficiency with Aconiti Lateralis Radix Praeparata (called Fuzi (FZ) in Chinese), with hot nature, as reference drug. Biochemical indexes in the material metabolism, energy metabolism, endocrine system, nervous system and nucleotide system were determined, then analyzed by additive, cluster and principal component analysis (PCA). Results The medicinal natures of oligosaccharides and amino acids fractions were attributable to plain and crude polysaccharides, volatile oils and triterpenoids fractions were attributable to mild warm. Conclusion The nature of FL was regarded as mild warm based on the old records of Chinese medicine and fractions of crude polysaccharides, volatile oils and triterpenoids might be the main substance basis for the warm nature of FL. It is the first time that substance basis of FL was elucidated from view point of medicinal nature.

The pharmacological and biological activities of steam-activated ginseng are greater than those of non-steamed ginseng. And also, the chemical profiling varies with different processing. To track the chemical constituents of white ginseng (WG), red ginseng (RG), and black ginseng (BG), ginsenosides and amino acids were comparatively analyzed in WG, RG, and BG. Twenty-three ginsenosides and twenty-nine amino acids were fast identified based on multiple ultra-performance liquid chromatography with mass spectrometry (UPLC-MS) methods. The results showed that during the steaming process of ginseng, ginsenosides transform into constituents of low polarity by hydrolysis, isomerization, and dehydration at C-20, and hydrolysis also occurs at C-3 or C-6. Relatively less attention has been paid to amino acids in WG, RG, and BG. The amino acids profiling of WG, RG, and BG showed the contents of amino acids were decreased during the steaming process. This simple and fast method provides possibility to monitor multiple components for the quality control and global evaluation of ginseng products during processing.

Ginsenosides and oligosaccharides were comparatively analyzed in WG, RG and BG. The HPLC fingerprints of ginsenosides and oligosaccharides were established to unravel the characteristics of ginsenosides and oligosaccharides. The primary ginsenosides (Rg1, Rb1, Re, Rc, Rb2 and Rd, etc.) in WG were higher than those in RG and BG, but the variety of ginsenosides in RG is highest and the non-polar rare saponins are higher than RG. Five kinds of saccharides encompassed fructose, glucose, sucrose, maltose and nystose, respectively, were determined in WG, RG and BG, disclosing that, the sucrose in WG is 1.4 times of that in RG and 119.6 times of that in BG; but the maltose in RG is 25.9 times of that in WG and 3.4 times of that in BG; the fructose in BG is 44 times that in WG and 18.3 times that in RG. The chemical reactions in the processing of ginseng were elucidated. It is for the first time that the ginsenosides and oligosaccharides were compared simultaneously in WG, RG and BG.

Fatigue is a kind of subhealth status and people paid much more attention on it. Ginseng is used to treating fatigue as a kind of qi -tonifying drug in Chinese medicine. In the traditional applications, there is a viewpoint that ginseng could not be used with semen raphani and supposed that semen raphani is a kind of qi regulating drug, which will reduce the qi invigorating effect of ginseng. However, the underlying combination mechanism of the two drugs remained unclear.The aim of this study is to explore whether ginseng can be used with semen raphani or not to remedy acute and chronic fatigue conditions.We used normal and weight-bearing swimming method combined with appetite control animals. The biochemical indexes in energy metabolism, antioxidant, regulating endocrine system and immunity capacities were performed to explore the antagonism effect of semen raphani on ginseng under acute and chronic fatigue conditions. The serum and urine metabolomics were investigated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Fecal flora was analyzed via 16S rRNA amplicon sequencing.The combination of ginseng with semen raphani have no influence on acute fatigue effect compared with ginseng alone. Both can improve the exhausted swimming time, the activity of GSH-Px, LDH and NaCompared with ginseng alone, the combination of ginseng with semen raphani can weaken the qi invigorating ability under chronic fatigue condition. The more ratios of semen raphani is in the combination of the two drugs, the less the power of treating chronic fatigue is. Compared with ginseng alone, the combination of ginseng with semen raphani have no influence on the qi invigorating ability under actue fatigue experiment. But the combination of ginseng with semen raphani will benefit for the "fireness" side-effect of ginseng.

Silicosis remains one of the most serious diseases worldwide, with no effective drug for its treatment. Our research results have indicated that arctiin and arctigenin could increase the mitochondrial membrane potential, which in turn reduces the production of reactive oxygen species (ROS), blocks the polarization of macrophages, and inhibits the differentiation of myofibroblasts to reduce oxidative stress, inflammation, and fibrosis. Further, our study revealed that arctiin and arctigenin suppressed the activation of NLRP3 inflammasome through the TLR-4/Myd88/NF-κB pathway and the silica-induced secretion of TNF-α, IL-1β, TGF-β, and α-SMA. Besides, the silica-induced increase in the levels of serum ceruloplasmin and HYP was also inhibited. Results of metabolomics indicated that arctiin and arctigenin could regulate the abnormal metabolic pathways associated with the development of silicosis, which involve pantothenate and CoA biosynthesis, cysteine and methionine metabolism, linoleic acid metabolism, and arginine and proline metabolism successively. Furthermore, the analysis of metabolomics, together with network topological analysis in different phases of silicosis, revealed that urine myristic acid, serum 4-hydroxyproline, and L-arginine could be regarded as diagnosis biomarkers in the early phase and formation of pulmonary fibrosis in the latter phases of silicosis. Arctiin and arctigenin could downregulate the increased levels of myristic acid in the early phase and serum 4-hydroxyproline in the latter phase of silicosis. Interestingly, the integration of TLR-4/NLRP3/TGF-β signaling and metabolomics verified the importance of macrophage polarization in the silicosis fibrosis process. To the best of our knowledge, this is the first study reporting that arctiin and arctigenin both can ameliorate silicosis effectively, and the former is a little stronger than its aglycone arctigenin because of its high oral bioavailability, low toxicity, and multimolecular active metabolites as determined by AdmetSAR and molecular docking analysis.

Carotenoids are the second most abundant natural compounds after chlorophyll. Chemically they are made of 8 isoprene units (typically tetra-terpenoids) joined in head to tail arrangement. They have several trivial names and still known by these names; however, their proper IUPAC naming initiated in the ’70s. Carotenoids are classified into various groups based on function, structure, source and end groups, etc. Typical carotenoids undergo oxidation, hydrogenation, isomerization, cyclization, and halogenation. These reactions convert them to their subgroups or derivatives. They play an essential role in plants and animals. In this chapter, readers will be able to know about carotenoids classification, chemistry, naming, types, association with other compounds, isomerism, chemical, physical and physicochemical properties.

Ginseng has been used for thousands of years, it is described as both a tonic for restoration of strength and a panacea. However, the adverse effect is also reported clinically. In the theory of Traditional Chinese Medicine, the occurrence of adverse reactions is closely related to warm property of ginseng, which can easily lead to fireness (, in Chinese). Several presumptions indicated that fireness of ginseng may be associated with the pathophysiology of inflammation, imbalance of metabolism, the disorder of hypothalamus-pituitary-adrenal axis, and hypothalamus-pituitary-thyroid axis.The tonifying effect of ginseng medicines was always focused on with little attention for their adverse effects. We selected red ginseng (RG), ginseng (GS), American ginseng (AG), and ginseng leaves (GL) as typical ginseng medicines to clarify correlations of adverse effect and tonifying effect of ginseng medicines.The RG, GS, AG, and GL decoctions were orally administered to rats for 30 days consecutively. The appearance indicators such as saliva secretion, urinary output, fecal moisture, heart rate were determined, and hair condition, nose color were also observed. Furthermore, some biochemical indexes such as IL-6, T3, T4, TSH, ACTH, CORT, Ach, DA, EPI, NE, SP, VIP, cAMP, cGMP, AQP-5, AMPK, and the activity of SOD, GSH-PX, NaThe study revealed the tonifying effects of ginseng medicines mainly on exciting nervous system, promoting immunity and antioxidative ability. While, the adverse effects were mainly associated with the abnormal nervous system, thyroid system, adrenal system, and oxidative stress. The GS group showed fireness symptoms, such as vertical and dirty hair, epistaxis, higher rectal temperature, lower salivary secretion, lower urinary output, lower fecal moisture. While the GL group showed the opposite symptoms. The levels of hormones, activities of the antioxidative enzyme, and NaThis is the first time to report the correlations between tonifying effects and adverse effects of four ginseng medicines. The present study demonstrated that the adverse effects of ginseng medicines mostly depended on their dosages, the higher dosage is, the more serious the adverse effects are. The adverse effects of ginseng and ginseng leaves are much more serious than red ginseng and American ginseng. The tendency of water regulation of ginseng and ginseng leaves was opposite may be related to their nature property.

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

Integrated metabolomics and proteomics analysis was carried out to study the effects of Poria and its split components (volatile oil, triterpenoid, oligosaccharide, amino acid, and crude polysaccharide) on rats of normal physiological model, hyperthyroidism model, and hypothyroidism model to explore the substance basis of Poria for hypothyroidism from the perspective of a holistic view in substance and energy metalism. The key pathways regulating substance and energy metabolism were screened, encompassing tricarboxylic acid cycle pathway, glycolysis/ gluconeogenesis pathways, biosynthesis of amino acid pathway, fatty acid biosynthesis pathway, pentose phosphate pathway, peroxisome proliferator-activated receptors pathway, etc Poria and its split components showed promoting effects on substance and energy metabolism in normal model, while showed amelioration effects on hypothyroidism model at different degrees, and had no significant improvement effects on hyperthyroidism in rats. Volatile oil, triterpenoid, and crude polysaccharide from Poria were regarded as substance basis of Poria ameliorating hypothyroidism other than hyperthyroidism. This work also revealed the feasibility of metabolomics and proteomics analysis to elucidate the effective substance basis of traditional Chinese medicine from a new viewpoint based on its effects on substance and energy metabolism.

Supplemental material, Supplementary Material 1, for Chemical Constituents of Tagetes patula and Their Neuroprotecting Action by Linlin Liu, Simin Luo, Miao Yu, Ahmed M. Metwaly, Xiaoku Ran, Chunyan Ma, Deqiang Dou and Decheng Cai in Natural Product Communications

Recent studies have revealed that the property of drug is mainly associated with the body's substance and energy metabolism. The present study aimed to evaluate the drug property of Poria, called Fuling (FL) in traditional Chinese medicine (TCM), in terms of its effects on the substance and energy metabolism in rat models of cold-deficiency and heat-deficiency syndromes, compared with Aconiti Lateralis Radix Praeparaia, called Fuzi (FZ) in TCM, with hot property, and Anemarrhenae Rhizoma, called Zhimu (ZM) in TCM, with cold property, as reference drugs, respectively. The appearance score, toe and rectal temperatures of the animals treated were assessed at different time points. Several indices in vivo correlated with substance and energy metabolism (glucokinas, phosphoglycerate kinase, cytochrome c reductase, cytochrome c oxydase, and Na+-K+-ATPase), endocrine system (triiodothyronine, thyroxine, and 17-hydroxycorticosteroid), nervous system (acetylcholin esterase), and cyclic nucleotide system were determined. The changes in appearance score and indices in vivo suggested the successful establishment of cold-deficiency and heat-deficiency syndrome models. FZ reversed the decreased levels of indices (substance and energy metabolism and endocrine system) and alleviated the syndrome of cold-deficiency model, and ZM showed obviously therapeutic effect on heat-deficiency syndrome (appearance score, substance and energy metabolism, and endocrine system). FL could alleviate cold-deficiency syndrome and raise the decreased levels of glucokinas, phosphoglycerate kinase, cytochrome c reductase and triiodothyronine in cold-deficiency model, but had no significant effect on heat-deficiency syndrome. Drug property of FL was inferred as trending to "flat and warm", which still need further study. It was advisable to adopt both cold-deficiency and heat-deficiency models to study the drugs with "flat" property.

Background: Panax ginseng Meyer which has been cultivated and grown naturally in mountainous forests is formally called “Lin-Xia-Shan-Shen” (LXSS), but when cultivated it is called garden ginseng (GG), according to the Chinese Pharmacopoeia (2015 edition). The medicinal value of LXSS is significantly higher than that of GG based on the clinical experience of TCM. This study aimed to evaluate the variety of chemical constituents in LXSS and GG. Methods: 18 LXSS and 6 GG samples were investigated using a UPLC-Q-TOF-MS technique. Results: the contents of 16 metabolites, mainly involved in the biosynthesis of rare ginsenosides (ginsenosides Rg3, -Rh1, -Rh2), galactose metabolism (myo-inositol), the citric cycle (citric acid and succinic acid), GABA shunt (GABA) and amino metabolism (alanine and aspartic acid), were higher in LXSS than in GG; while 14 metabolites, mainly involved in starch and sucrose metabolism (fructose and sucrose), amino metabolism (tryptophan, proline, dencichine and pyroglutamic acid) and campesterol biosynthesis (campesterol), were lower in LXSS than in GG. For LXSS with different growing years, 5 metabolites showed a tendency to increase dependent on the number of years, and these were related mainly to galactose metabolism (melibiose), the citric cycle (malic acid), fatty acid metabolism (2-hydroxy stearic acid); while 5 metabolites showed a tendency to decrease on ascending the grades, and these were related to sucrose metabolism (fructose and sucrose), fatty acid metabolism (2-hydroxy hexadecanoic acid) and campesterol biosynthesis (campesterol). Conclusion: this proposed analytical method coupled with multivariate analysis is fast, accurate, and reliable for discriminating GG and high cultivation ages of LXSS samples.

Background: the present study was to investigate the neuroprotective effect of arctigenin, the major active component of a traditional Chinese medicine “Arctii Fructus”, against PD in a rat model induced by rotenone. Materials and methods: in the present study, rotenone was injected subcutaneously in the backs of rats to mimic the progressive neurodegenerative nature of PD and arctigenin was administered. Behavioral analyses including a grid test, bar test and open-field test were used to evaluate motor activities and behavioral movement abilities. Energy metabolism indexes including oxygen consumption, carbon dioxide production, heat production and energy expenditure were measured via a TSE phenoMaster/LabMaster animal monitoring system. Immunohistochemistry was performed to detect the staining of TH and the expression of α-synuclein in substantia nigra (SN). The effect of arctigenin on oxidative stress was evaluated by the levels of GSH and MDA, and activities of SOD and GSH-Px. The levels of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, IFN-γ and PGE2, the expression of Iba-1 and GFAP, and the impression of inflammatory mediators such as COX-2 and NF-κB in the SN were measured to evaluate the effect on the inflammation of SN area induced by rotenone. Results: compared with the ROT group, the deadlock time of rats treated with arctigenin was significantly shortened and the score of locomotor activity increased in the behavioral test; the number of TH+ positive DA neurons of the arctigenin treated group was increased and α-synuclein immunopositive was decreased; the level of GSH and activities of SOD and GSH-Px in the arctigenin-treated group were significantly increased; arctigenin administration induced a significant decrease in the MDA level; arctigenin also significantly decreased the levels of IL-6, IL-1β, TNF-α, IFN-γ and PGE2 and reduced the impression of COX-2 and NF-κB in SN; treatment with arctigenin decreased microglia and astrocyte activation evidenced by the reduced expression of Iba-1 and GFAP. Conclusion: the findings demonstrated that arctigenin can improve the behavior changes of PD rats and the damage of DA neurons. The oxidative stress and inflammation involved in the pathogenesis of PD and arctigenin may protect DA neurons through its potent antioxidant and anti-inflammatory activities.

To explore the effect of rhizosphere soil factors on the morphological characteristics and ginsenosides of mountainous forest cultivated ginseng (MFCG) and its origin traceability as well as distinguishing from garden ginseng (GG) by the stable isotope ratios (δ13C and δ15N), high-performance liquid chromatography with diode array detector (HPLC-DAD) technique was adopted to investigate the ginsenosides of MFCG; The contents of 25 mineral elements in MFCG and its rhizosphere soils were determined by inductively coupled plasma mass spectrometry (ICP-MS), inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic absorption spectrometry and the other factors, including pH and available N, P and K were also measured; The δ13C and δ15N were determined by the elementary analyzer (EA)-Isotope ratio mass spectrometer (IRMS). Results indicated that the rhizosphere soil factors closely affected the MFCG quality in both morphological characteristics and chemical composition. The contents of mineral elements in MFCG and its rhizosphere soils from different origins could be used for geographical origin traceability, especially Ni and Co for MFCG and Ba and Sn for its rhizosphere soils. In addition, MFCG and the GG could be completely distinguished with the δ15N/‰ and δ15N/δ13C, especially the former. It is for the first time that the effects of the rhizosphere soil minerals on the quality of MFCG and its distinguishing from GG by the stable isotope technique were explored.

HuanglianJiedu decoction (HJD) is a classic prescription for heat-clearing away and detoxifying, which is used for the clinical treatment of sepsis, due to sepsis refers to the systemic inflammatory response induced by infection in western medicine, and infection belongs to the category of poison-heat syndrome in traditional Chinese medicine.Previous study had elucidated the effective components from HJD with high affinity to lipid A, which can generate the release of pro-inflammatory-cytokines, resulting in sepsis. Now the anti-sepsis activities of these compounds were evaluated.Immunofluorescence, immunohistochemical staining, ELISA and MTT methods were used to evaluated these compounds.Immunofluorescence analysis evaluated the effects of compounds on the binding of FITC-LPS to RAW264.7 cells, and showed the fluorescence intensity was significant attenuated in geniposides, palmatine, baicalin and berberine groups (64 and 128 μg/mL) compared with model group (p 0.05), which showed these compounds inhibit the combination of LPS with receptor of cells; immunohistochemical staining and ELISA method showed the TLR4 receptor expression, IL-6 and TNF-α levels were significant decreased in the groups treated with compounds, indicating that geniposides, baicalin, palmatine and berberine can play the role of anti-sepsis by inhibiting the expression of TLR4, the releasing of IL-6 and TNF-α; MTT assay showed that palmatine and berberine had a weak effect on cell viability, while others not, indicating that the compounds have protective activity.It could be concluded the high affinity binding between these compounds and lipid A may be an important basis for its anti-LPS activity in vitro.

Background: Berberine is a natural isoquinoline alkaloid possessing various pharmacological effects, particularly apparent in the treatment of diarrhea, but the underlying mechanism remains unclear. Smooth muscle myosin light-chain kinase (MLCK) plays a crucial role in the smooth muscle relaxation-contraction events, and it is well known that berberine can effectively depress the contraction of smooth muscle. Hence, whether berberine could inhibit MLCK and then depress the smooth muscle contractility might be researched. Objective: The purpose of this study is to investigate the effects of berberine on MLCK. Based on this, the contractility of gastro-intestine, catalysis activity of MLCK, and molecular docking are going to be evaluated. Materials and Methods: The experiment of smooth muscle contraction was directly monitored the contractions of the isolated gastrointestine by frequency and amplitude at different concentration of berberine. The effects of berberine on MLCK were measured in the presence of Ca2+-calmodulin, using the activities of 20 kDa myosin light chain (MLC20) phosphorylation, and myosin Mg2+-ATPase induced by MLCK. The docking study was conducted with expert software in the meantime. Results: The phosphorylation of myosin and the Mg2+-ATPase activity is reduced in the presence of berberine. Moreover, berberine could inhibit the contractibility of isolated gastric intestine smooth muscle. Berberine could bind to the ATP binding site of MLCK through hydrophobic effect and hydrogen bonding according to the docking study. Conclusion: The present work gives a deep insight into the molecular mechanism for the treatment of diarrhea with berberine, i.e., berberine could suppress the contractility of smooth muscle through binding to MLCK and depressing the catalysis activity of MLCK. SUMMARY Berberine significantly reduced the amplitude of contraction in isolated duodenum and gastric strips in ratsBerberine inhibited the phosphorylated extents of MLC20 and Mg2+-ATPase activity of phosphorylated myosin induced by MLCKBerberine binds to the ATP binding site of MLCK by hydrophobic effect and hydrogen bondingBerberine may modulate contraction of smooth muscle by inhibiting MLCK. Abbreviations used: MLCK: Myosin light chain kinase; MLC20: 20 KDa regulating myosin light chain; CaM: Calmodulin.

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3&ndash, 16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 &mu, mol/L and 30.43 &mu, mol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism of T. patula by metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides of T. patula could alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-&alpha, Besides, both could enhance Na+/K+-ATPase activity, decrease the O2 consumption, CO2 production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides of T. patula might be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism.

The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism of T. patula by metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides of T. patula could alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-α. Besides, both could enhance Na+/K+-ATPase activity, decrease the O2 consumption, CO2 production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides of T. patula might be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism.

Ethnopharmacological relevance Type 2 diabetes mellitus (T2DM) regarded as a “hot” disease in traditional Chinese medicine (TCM). Accordingly, TCM uses a cold drug or formula such as the Chinese herbal formulae “Yitangkang” (YTK) as a treatment. YTK exhibited a good clinical antidiabetic effect in several experiments. The correlation between the properties of a TCM drug or formula and its ability to regulate the substance metabolism, the energy metabolism and the endocrine system has been proven. Aim of the study The present study aiming to evaluate the mechanism of antidiabetic action of YTK from the above perspective. Materials and methods Three groups of streptozotocin (STZ)-diabetic rats have been treated with YTK at oral doses of 56 g/kg/d, 28 g/kg/d and 14 g/kg/d for 28 days using metformin as a reference drug. After treatment, several indices correlated with energy metabolism (superoxide dismutase, glutathione peroxidase, lactic dehydrogenase, adenotriphos, creatine phosphate kinase, AMPK, Na+-K+-ATPase and Respiratory Chain Complex I, II, III, IV), substance metabolism (hepatic glycogen, acetyl-coenzyme A, pyruvic acid, adipose triglyceride lipase, triglycerides, high-density lipoproteins, low-density lipoproteins, malonyldialdehyde), endocrine system (triiodothyronine, thyroxine, 17-hydroxycorticosteroid) and cyclic nucleotide system (cyclic adenosine monophosphate, cyclic guanosine monophosphate) have been determined. The specialty and tendency of YTK's effects were analyzed to elucidate its property and mechanism of action according to the theory of TCM. Results Our findings showed that the formulae YTK could effectively regulate the levels of blood glucose, HbA1c, glucagon-like peptide-1, and significantly down-regulate the substance metabolism, energy metabolism and endocrine system indices of the diabetic rats. Conclusion These results were consistent with the TCM description of YTK as a “cold” treatment. It could provide an effective way to interpret the scientific connotation and comprehensive system of the Chinese herbal formulae.

Ethnopharmacological relevance Ginseng is an herbal medicine used worldwide that possesses a wide range of pharmacological activities. However, its side effects are rarely discussed. The experience of Chinese medicine has revealed that taking ginseng at a high dose chronically can cause fireness, i.e., the ginseng-abuse syndrome. Here, we explored the mechanism of ginseng's fireness by comparing the energy metabolism of mice affected by red ginseng (RG), ginseng (GS), ginseng leaves (GL) and American ginseng (AG), which exhibit different drug properties according to the theory of TCM. Materials and methods KM mice were randomly divided into five groups (n≥30 per group) and administered distilled water or drugs, respectively. Mice receiving RG, GS, or GL received 4.5 g/(kg day), while the mice receiving AG received 3 g/(kg day). Control mice received distilled water. The duration of exposure for all groups was 31 days. The mice's physical characteristics, such as eye condition, rectal temperature, saliva secretion, urine, stool weight, blood coagulation time and swimming time, were measured at different times after administration. Energy metabolism indexes were measured via TSE phenoMaster/LabMaster animal monitoring system, including the mice' 24 h oxygen consumption (VO2), carbon dioxide production (VCO2), heat production (H) and energy expenditure (EE). Biochemical indices were measured by ultraviolet spectrophotometer and microplate reader, including pyruvic acid content in serum and succinate dehydrogenase (SDH) activity, lactate dehydrogenase (LDH) activity, the Na+-K+-ATPase activity and the content of glycogen in the liver tissue. Results After 31 days of drug administration, mice in the RG and GS groups exhibited obviously more eye secretions, less saliva secretion and less urine. Compared with the control group, the swimming times of mice in the GS, AG and GL groups were significantly prolonged; the clotting time of mice in the GL was extended significantly; VCO2, H and EE of mice in the GS group were obviously increased; Pyruvate content of mice in the RG group showed an initial decrease followed by an increase; SDH activity of mice in the AG and GL groups was significantly inhibited; LDH activity of the mice showed no significant difference among different groups; Na+-K+-ATP enzyme activity of the RG and GS groups showed up-regulation initially and then down-regulation; the content of hepatic glycogen of mice in the GS and GL groups increased significantly. Conclusion The results demonstrated that RG and GS with their warm drug nature could enhance the body’s energy metabolism to produce their dryness to the body. The liver Na+-K+-ATP enzyme activity may be the primary index for indicating the fireness of ginseng. In addition, our results demonstrated that ginseng, especially red ginseng, is not suitable for long time application with a higher dose.

Objective Huangqi Injection is a preparation with an extract of Astragali Radix which has a long history of being used as a tonic to strengthen the body's immunity. Anaphylaxis and hemolysis are two main adverse drug reaction (ADR) of injections. Our study was aimed to establish an approach for the (ADR) prediagnosis of Huangqi Injection. Methods An in vitro model for anaphylactoid assay of Huangqi Injection based on the release rate of histamine and β-hexosaminidase of RBL-2H3 cells induced by injections and a colorimetric method based on the detection of hemoglobin resulted in the erythrocyte hemolysis for prediagnostic assaying the hemolytic ADR of injections were established. Results Both histamine and β-hexosaminidase are the anaphylactiod mediators, but β-hexosaminidase release induced by Huangqi Injection could not be determined by spectrophotometry due to the interference of the injection itself. In addition, normal hemolysis and abnormal hemolysis were discovered during the experiment. The fingerprints and tannins in different batches of injections showed obvious differences, indicating that the content of tannins was related to abnormal hemolysis and higher histamine-secreting from RBL-2H3 cells. Conclusion The results indicate that the hemolytic assaying method is not only suitable for prediagnostic assaying of hemolytic ADR of herbal medicine injection, but also partly reflects the anaphylaxis of herbal injections, and tannins may be the major factors causing abnormal hemolysis.

Two novel flavonoids (1, 2) and 3 known compounds (3-5) were isolated from the flowers and whole plant of Tagetes patula L., and their structures were elucidated by means of ultra-high performance liquid chromatography with electrospray ionization, coupled to quadrupole-time-of-flight/mass spectrometry,1H and13C-nuclear magnetic resonance (NMR), as well as 2-dimensional-NMR (heteronuclear single quantum correlation and heteronuclear multiple bond correlation) and chemical methods. In addition, all the compounds were examined for their neuroprotective action on the injury of SH-SY5Y cells induced by glutamate, indicating that the protective effect of these compounds on glutamate-induced SH-SY5Y cell was marigold biflavone > patuletin > quercetin > kaempferol-3- O-β-d-glucoside > patuletin-3- O-α-l-arabinopyranoside. Thus, it could be concluded that flavonoids played a key role in the neuroprotective action of T. patula.

Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction.

The chemical constituents of 95% EtOH extract of yacon leaves were separated to yield two new sesquiterpene lactones, together with three known compounds. The two new compounds were characterized to be 8β-angeloyloxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (1) and 8β-(3-methylbut-2-enoyl) oxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (2) on the basis of NMR spectra, HR-MS and other spectroscopic methods. The cytotoxicity of compounds 1–5 were evaluated on human hepatoma cell Bel-7402 and all the compounds showed moderate cytotoxicity.