Metagenomics approach the intestinal microbiome structure and function in the anti-H1N1 of a traditional chinese medicine acid polysaccharide.

Ephedra sinica Stapf polysaccharide is a pure acidic uniform polysaccharide extracted from the traditional Chinese medicine Ephedra sinica Stapf. In our past research, it was found that it has anti-inflammatory response and suppresses immunity. Therefore, in this experiment, mice were infected with FM1 virus, treated with Ephedra sinica Stapf polysaccharide, and metagene sequencing was used to sequence the mouse intestinal contents. As a result, we found that Ephedra sinica Stapf polysaccharide has obvious therapeutic effect on acute lung injury caused by H1N1. In the intestinal flora, the abundance of Lactobacillales and Bifidobacteriaceae increased significantly, and the metabolome increased significantly in the KEGG pathway. The intestinal flora may be an important target of Ephedra sinica Stapf polysaccharides metabolism against H1N1.

A Novel Antihypertensive Derived from Adlay (Coix larchryma-jobi L. var. ma-yuen Stapf) Glutelin.

Our previous studies have shown that Coix glutelin pepsin hydrolysate can effectively inhibit angiotensin converting enzyme (ACE) activity in vitro. The main purpose of this study was to obtain potent anti-hypertensive peptides from Coix glutelin. The Coix glutelin hydrolysates (CGH) were prepared by pepsin catalysis and further separated by an ultrafitration (UF) system, gel filtration chromatography (GFC) and reversed-phase high performance liquid chromatography (RP-HPLC). As a result, the sub-fraction F5-3 had the highest ACE-inhibitory activity. Six ACE inhibitory peptides were identifiedusing nano-liquid chromatography coupled to tandem mass spectrometry. The most potent peptide GAAGGAF (IC50 = 14.19 µmol·L-1) was finally obtained by further molecular simulation screening and a series of division and optimization. Single oral administration of synthesized GAAGGAF at 15 mg/kg body weight (BW) in spontaneously hypertensively rats (SHR) could reduce the systolic blood pressure (SBP) around 27.50 mmHg and blood pressure-lowering effect lasted for at least 8 h. The study demonstrated for the first time that the ACE inhibitory peptide GAAGGAF from Coix glutelin has a significant antihypertensive effect, and it could be a good natural ingredient for pharmaceuticals against hypertension and the related diseases.

Characterization of aromatic aminotransferases from Ephedra sinica Stapf.

Ephedra sinica Stapf (Ephedraceae) is a broom-like shrub cultivated in arid regions of China, Korea and Japan. This plant accumulates large amounts of the ephedrine alkaloids in its aerial tissues. These analogs of amphetamine mimic the actions of adrenaline and stimulate the sympathetic nervous system. While much is known about their pharmacological properties, the mechanisms by which they are synthesized remain largely unknown. A functional genomics platform was established to investigate their biosynthesis. Candidate enzymes were obtained from an expressed sequence tag collection based on similarity to characterized enzymes with similar functions. Two aromatic aminotransferases, EsAroAT1 and EsAroAT2, were characterized. The results of quantitative reverse transcription-polymerase chain reaction indicated that both genes are expressed in young stem tissue, where ephedrine alkaloids are synthesized, and in mature stem tissue. Nickel affinity-purified recombinant EsAroAT1 exhibited higher catalytic activity and was more homogeneous than EsAroAT2 as determined by size-exclusion chromatography. EsAroAT1 was highly active as a tyrosine aminotransferase with α-ketoglutarate followed by α-ketomethylthiobutyrate and very low activity with phenylpyruvate. In the reverse direction, catalytic efficiency was similar for the formation of all three aromatic amino acids using L-glutamate. Neither enzyme accepted putative intermediates in the ephedrine alkaloid biosynthetic pathway, S-phenylacetylcarbinol or 1-phenylpropane-1,2-dione, as substrates.

Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro.

AIMS: The emergence of multidrug-resistant (MDR) Staphylococcus aureus is a challenge for the treatment of infections. We report here the antimicrobial activity of artonin I against MDR Staph. aureus, its mechanism of reversal of resistance and synergistic effects by combinational therapy. METHODS AND RESULTS: Artonin I, a flavonoid obtained from Morus mesozygia Stapf., inhibited the bacterial efflux pump and induced depolarization of the cell membrane. To study the dose-dependent production of reactive oxygen species in MDR cells by artonin I, lucigenin chemiluminescence assay was employed. Reversal of multidrug resistance by artonin I, in combination with antibiotics, was measured by a fractional inhibitory concentration index assay. The effect of artonin I on ultrastructural features was studied by microscopy. Artonin I increased the penetration of ethidium bromide by blocking the efflux mechanism. It also helped anionic probe DiBAC4 (3) to bind with the lipid-rich cellular components by causing depolarization of the cell membrane. Artonin I reversed multidrug resistance and increased the susceptibility of existing antibiotics by lowering their minimum inhibitory concentrations (MICs). CONCLUSIONS: Artonin I was identified both as a new antibacterial agent and a helper molecule to potentiate the action of otherwise inactive antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Artonin I can be developed as potential antimicrobial and resistance reversal agent.

Effect and mechanisms of Gambi-jung against high-fat diet-induced cardiac apoptosis in mice.

Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Ephedra sinica Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of uncoupling protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, optic atrophy protein 1, and fission protein 1. Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration.

Ethnopharmacology, chemical composition and functions of Cymbopogon citratus.

Cymbopogon citratus in the gramineous family, also known as lemongrass (LG), is a perennial herb. LG, a drug and food homologous medicine, has a widely recorded medicinal value and food applications. To date, 158 LG compounds have been reported, including terpenoids, flavonoids, phenolic acids. Pharmacological and clinical studies have indicated that LG has antibacterial, neuroprotective, hypoglycemic, hypotensive, anti-inflammatory, and anti-tumor effects. This article reviews LG in ethnopharmacology, chemical composition, pharmacology, food, medicine, and daily chemical applications to provide a basis for the subsequent development of food and medicine.

Coix Sprouts Affect Triglyceride Metabolism in Huh7 Cells and High-Fat Diet-Induced Obese Mice.

Lipolysis is the hydrolysis of triglycerides (TGs), commonly known as fats. Intracellular lipolysis of TG is associated with adipose triglyceride lipase (ATGL), which provides fatty acids during times of metabolic need. The aim of this study was to determine whether Coix lacryma-jobi L. var. ma-yuen Stapf (Coix) sprouts (CS) can alleviate obesity through lipolysis. Overall, we investigated the potential of CS under in vitro and in vivo conditions and confirmed the underlying mechanisms. Huh7 cells were exposed to free fatty acids (FFAs), and C57BL/6J mice were fed a 60% high-fat diet. When FFA were introduced into Huh7 cells, the intracellular TG levels increased within the Huh7 cells. However, CS treatment significantly reduced intracellular TG levels. Furthermore, CS decreased the expression of Pparγ and Srebp1c mRNA and downregulated the mutant Pnpla3 (I148M) mRNA. Notably, CS significantly upregulated ATGL expression. CS treatment at a dose of 200 mg/kg/day resulted in a significant and dose-dependent decrease in body weight gain and epididymal adipose tissue weight. Specifically, the group treated with CS (200 mg/kg/day) exhibited a significant modulation of serum lipid biomarkers. In addition, CS ameliorated histological alterations in both the liver and adipose tissues. In summary, CS efficiently inhibited lipid accumulation through the activation of the lipolytic enzyme ATGL coupled with the suppression of enzymes involved in TG synthesis. Consequently, CS show promise as a potential anti-obesity agent.

A comprehensive study of Ephedra sinica Stapf-Schisandra chinensis (Turcz.) Baill herb pair on airway protection in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedra sinica Stapf (Mahuang) and Schisandra chinensis (Turcz.) Baill (Wuweizi) are commonly utilized in traditional Chinese medicine for the treatment of cough and asthma. The synergistic effect of Mahuang-Wuweizi herb pair enhances their efficacy in alleviating respiratory symptoms, making them extensively employed in the management of respiratory disorders. Although previous studies have demonstrated the therapeutic potential of Mahuang-Wuweizi in pulmonary fibrosis, the precise mechanism underlying their effectiveness against asthma remains elusive. AIM OF THE STUDY: The objective of this study is to investigate the mechanism underlying the preventive and therapeutic effects of Mahuang-Wuweizi herb pair on asthma progression, focusing on airway inflammation and airway remodeling. MATERIALS AND METHODS: The active constituents and potential mechanisms of Mahuang-Wuweizi in the management of asthma were elucidated through network pharmacology analysis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to detect the main components of Mahuang-Wuweizi decoction. A rat model of bronchial asthma was established, and the effects of Mahuang-Wuweizi were investigated using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) staining, enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The results of network pharmacological prediction showed that Mahuang had 22 active components and Wuweizi had 8 active components, with 225 potential targets. 1159 targets associated with asthma and 115 targets that overlap between drugs and diseases were identified. These include interleukin-6 (IL-6), tumor necrosis factor (TNF), Tumor Protein 53, interleukin-1ß (IL-1ß), as well as other essential targets. Additionally, there is a potential correlation between asthma and Phosphatidylinositol 3 kinase (PI3K)/Protein Kinase B (AKT) signaling pathway, calcium ion channels, nuclear factor-kappa B (NF-κB) signaling pathway, and other signaling pathways. The animal experiment results demonstrated that treatment with Mahuang and Wuweizi, in comparison to the model group, exhibited improvements in lung tissue pathological injury, reduction in collagen fiber accumulation around the airway and proliferation of airway smooth muscle, decrease in concentration levels of IL-6, TNF-α and IL-1ß in lung tissue, as well as alleviation of airway inflammation. Furthermore, Mahuang and Wuweizi suppressed the expression of phospholipase C (PLC), transient receptor potential channel 1 (TRPC1), myosin light chain kinase (MLCK), NF-κB P65 protein in ovalbumin (OVA)-sensitized rat lung tissue and downregulated the mRNA expression of PLC, TRPC1, PI3K, AKT, NF-κB P65 in asthmatic rats. These findings were consistent with network pharmacological analysis. CONCLUSION: The results show that the synergistic interaction between Mahuang and Wuweizi occur, and they can effectively reduce airway remodeling and airway inflammation induced by inhaling OVA in bronchial asthma rats by inhibiting the expression of PLC/TRPC1/PI3K/AKT/NF-κB signaling pathway. Therefore, Mahuang and Wuweizi may be potential drugs to treat asthma.

Ardisia gigantifolia stapf (Primulaceae): A review of ethnobotany, phytochemistry, pharmacology, clinical application, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ardisia gigantifolia Stapf, known as Zou-ma-tai (in Chinese), is a traditional folk medicine, which was commonly used by Dong, Jing, Li, Maonan, Miao, Mulam, Yao, and Zhuang people. The main use of A. gigantifolia is the treatment of rheumatoid arthritis, gouty arthritis, fractures, osteoproliferation, traumatic injuries, gynecological, and neurological diseases. Current studies have shown that the plant has various bioactive components, especially gigantifolinol, which has anti-tumor, anti-inflammatory, anti-tuberculosis, and neuroprotective activities. However, to date, few reviews have been made to summarize A. gigantifolia's related studies. AIMS OF THE REVIEW: This review aimed to summarize the traditional use, phytochemistry, pharmacology, clinical applications, and toxicity of A. gigantifolia, which expect to provide theoretical support for future utilization and highlight the further investigation of this vital plant. MATERIALS AND METHODS: The information related to A. gigantifolia were collated by surveying the traditional medicine books, ethnomedicinal publications, and searching academic resource databases including Web of Science, SciFinder, Springer Link, Pub Med, Science Direct, CNKI, and CQVIP database. RESULTS: A. gigantifolia has been used as a traditional folk medicine for more than 400 years in China. Different parts of the plant, including the aerial part, root, rhizome, and leaf, are mainly used as herbal medicine to treat rheumatoid arthritis, traumatic injuries, gynecological, etc. Currently, 165 compounds have been identified from the plant, including triterpenes, phenolics, coumarins, quinones, volatile oil, and sterols, 137 of which were identified from the rhizome parts. Pharmacological research showed that A. gigantifolia has various bioactivities, such as anti-tumor, anti-inflammatory, anti-oxidant, anti-thrombus, anti-tuberculosis, cough expectorant, and neuroprotective activities. Clinical studies have shown that the plant has no toxic side effects. In vivo administration at the maximum dose was not lethal, indicating the plant's safety. CONCLUSION: To date, most bioactive compounds are identified from the rhizomes of A. gigantifolia, which pharmacological activity and clinical observational studies have validated the plant's traditional use as a treatment for rheumatoid arthritis. It would be helpful to verify the mechanism of some components in vivo, such as gigantifolinol. Moreover, the plant's triterpenoid saponins demonstrated valid anti-tumor effects, especially the AG4 and AG36 compounds, which were shown to have anti-breast cancer effects both in vitro and in vivo. Further research on these components, including molecular mechanisms and in vivo metabolic regulation, needs to be confirmed.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology.

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf in the Gramineae family. Coix seed has a sweet, light taste, and a cool nature. Coix seed enters the spleen, stomach, and lung meridians. It has the effects of promoting diuresis and dampness, strengthening the spleen to prevent diarrhea, removing arthralgia, expelling pus, and detoxifying and dispersing nodules. It is used for the treatment of edema, athlete's foot, poor urination, spleen deficiency and diarrhea, dampness and obstruction, lung carbuncle, intestinal carbuncle, verruca, and cancer. The medicinal and health value is high, and it has been included in the list of medicinal and food sources in China, which has a large development and application space. This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times, aiming to provide reference for further research on Coix seed and contribute to its clinical application and development. Through the analysis of the traditional Chinese patent medicines, and simple preparations and related health food of Coix seed queried by Yaozhi.com, the source, function, and dosage form of Coix seed were comprehensively analyzed, with a view of providing a reference for the development of Coix seed medicine and food.

Anti-colorectal cancer of Ardisia gigantifolia Stapf. and targets prediction via network pharmacology and molecular docking study.

BACKGROUND: Ardisia gigantifolia Stapf. (AGS), a Chinese folk medicine widely grows in the south of China and several studies reported that AGS could inhibit the proliferation of breast cancer, liver cancer, and bladder cancer cell lines. However, little is known about its anti-colorectal cancer (CRC) efficiency. METHODS: In the present study, a combination of MTT assay, network pharmacological analysis, bioinformatics, molecular docking, and molecular dynamics simulation study was used to investigate the active ingredients, and targets of AGS against CRC, as well as the potential mechanism. RESULTS: MTT assay showed that three kinds of fractions from AGS, including the n-butanol extract (NBAGS), ethyl acetate fraction (EAAGS), and petroleum ether fraction (PEAGS) significantly inhibited the proliferation of CRC cells, with the IC50 values of 197.24, 264.85, 15.45 µg/mL on HCT116 cells, and 523.6, 323.59, 150.31 µg/mL on SW620 cells, respectively. Eleven active ingredients, including, 11-O-galloylbergenin, 11-O-protocatechuoylbergenin, 11-O-syringylbergenin, ardisiacrispin B, bergenin, epicatechin-3-gallate, gallic acid, quercetin, stigmasterol, stigmasterol-3-o-ß-D-glucopyranoside were identified. A total of 173 targets related to the bioactive components and 21,572 targets related to CRC were picked out through database searching. Based on the crossover targets of AGS and CRC, a protein-protein interaction network was built up by the String database, from which it was concluded that the core targets would be SRC, MAPK1, ESR1, HSP90AA1, MAPK8. Besides, GO analysis showed that the numbers of biological process, cellular component, and molecular function of AGS against CRC were 1079, 44, and 132, respectively, and KEGG pathway enrichment indicated that 96 signaling pathways in all would probably be involved in AGS against CRC, among which MAPK signaling pathway, lipid, and atherosclerosis, proteoglycans in cancer, prostate cancer, adherens junction would probably be the major pathways. The docking study verified that AGS had multiple ingredients and multiple targets against CRC. Molecular dynamics (MD) simulation analysis showed that the binding would be stable via forming hydrogen bonds. CONCLUSION: Our study showed that AGS had good anti-CRC potency with the characteristics of multi-ingredients, -targets, and -signaling pathways.

Screening and Elucidation of Chemical Structures of Novel Mammalian α-Glucosidase Inhibitors Targeting Anti-Diabetes Drug from Herbals Used by E De Ethnic Tribe in Vietnam.

Among ten extracts of indigenous medicinal plants, the MeOH extract of Terminalia triptera Stapf. (TTS) showed the most efficient mammalian α-glucosidase inhibition for the first time. The data of screening bioactive parts used indicated that the TTS trunk bark and leaves extracts demonstrated comparable and higher effects compared to acarbose, a commercial anti-diabetic drug, with half-maximal inhibitory concentration (IC50) values of 181, 331, and 309 µg/mL, respectively. Further bioassay-guided purification led to the isolation of three active compounds from the TTS trunk bark extract and identified as (-)-epicatechin (1), eschweilenol C (2), and gallic acid (3). Of these, compounds 1 and 2 were determined as novel and potent mammalian α-glucosidase inhibitors. The virtual study indicated that these compounds bind to α-glucosidase (Q6P7A9) with acceptable RMSD values (1.16-1.56 Å) and good binding energy (DS values in the range of -11.4 to -12.8 kcal/mol) by interacting with various prominent amino acids to generate five and six linkages, respectively. The data of Lipinski's rule of five and absorption, distribution, metabolism, excretion and toxicity (ADMET)-based pharmacokinetics and pharmacology revealed that these purified compounds possess anti-diabetic drug properties, and the compounds are almost not toxic for human use. Thus, the findings of this work suggested that (-)-epicatechin and eschweilenol C are novel potential mammalian α-glucosidase inhibitor candidates for type 2 diabetes treatment.

Extract of Ephedra sinica Stapf Induces Browning of Mouse and Human White Adipocytes.

Browning of adipocytes using herbal extracts is an attractive and realistic strategy for obesity treatment. Ephedra sinica Stapf (E. sinica) is an Asian traditional medicine known to activate brown adipocytes. To evaluate the effect of E. sinica (EEs) on the browning of white adipocytes, expression levels of browning markers, including uncoupling protein 1 (UCP1), were determined using qPCR, Western blot, and immunocytochemistry after mature mouse inguinal preadipocyte (mIPA) and human adipose-derived stem cells (hADSCs) were treated with EEs. In addition, mitochondrial activity was determined by analyzing MitoTracker staining, mtDNA copy number, and oxygen consumption rate (OCR). Treatment with EEs suppressed lipid accumulation and expression levels of adipogenic markers, including Pparg, during mIPA differentiation. In mature mIPA and hADSCs browning markers, including Ucp1, were up-regulated by EEs. In addition, EEs increased expression of mitochondrial genes, mtDNA copy number, and OCR. EEs showed a dual function: inhibiting adipogenesis in immature preadipocytes, and promoting thermogenesis via browning in mature white adipocytes. Therefore, E. sinica is a potential herb for regulating energy metabolism by inducing the browning process.

Contortamide, a new anti-colon cancer cerebroside and other constituents from Tabernaemontana contorta Stapf (Apocynaceae).

A new cerebroside, Contortamide (1) together with nine known compounds spegatrine (2), affinisine (3), Nb-methylaffinisine (4), ursolic acid (5), α-amyrin (6), bauerenol acetate (7), lupeol (8), betulinic acid (9) and ß-sitosterolglycoside (10) were isolated from the trunk bark of Tabernaemontana contorta Stapf. The new compound 1 showed significant activity against Caco-2 colon cancer cells with the MTT method. Compounds 1-4 and 6-9 were isolated for the first time from this species.

Anti-inflammatory and anti-rheumatic activities in vitro of alkaloids separated from Aconitum soongoricum Stapf.

The aim of the present study was to investigate the cell proliferation-inhibiting and anti-rheumatic activities of chemical components from Aconitum soongoricum Stapf. Chemical constituents of Aconitum soongoricum Stapf. were separated and purified by silica gel and Sephadex LH-20 chromatography. Structure was identified by spectroscopic technique, and physical/chemical properties were analyzed. The following four compounds were identified: i) Aconitine, ii) songorine, iii) 16, 17-dihydro-12ß, 16ß-epoxynapelline, and iv) 12-epi-napelline. Cell Counting kit-8 assay was performed to assess cell proliferation. ELISA was conducted to determine the cytokine contents, and reverse transcription-quantitative polymerase chain reaction and Western blot analysis were performed to detect the mRNA and protein expression levels. Compared with the lipopolysaccharide (LPS) group, the contents of IL-6, IL-1ß, TNF-α and PGE-2 in the culture supernatant were significantly declined in the leflunomide + LPS and intervention+LPS groups, as well as the mRNA expression levels of HIF-1α, VEGFA and TLR4. Treatments with songorine, benzoylaconine and aconitine (at different concentrations) significantly inhibited the proliferation of HFLS-RA cells. Compared with the LPS group, the contents of PGE-2, IL-6, IL-1ß and TNF-α in the culture supernatant were significantly decreased in the intervention groups, and the mRNA expression levels of TLR4, HIF-1α and VEGFA in the cells in the intervention groups. Songorine, benzoylaconine and aconitine from Aconitum soongoricum Stapf. have anti-rheumatic activities in vitro, which may inhibit the proliferation of HFLS-RA cells, and the underlying mechanisms may be associated with inhibiting the inflammatory cytokine production and downregulating the expression levels of HIF-1α, VEGF and TLR4.

Voacafrines A-N, aspidosperma-type monoterpenoid indole alkaloids from Voacanga africana with AChE inhibitory activity.

Fourteen undescribed monoterpenoid indole alkaloids, voacafrines A-N, along with 7 known monoterpenoid indole alkaloids were isolated from the seeds of Voacanga africana Stapf. Among them, voacafrines A-G were aspidosperma-aspidosperma type bisindole alkaloids, while voacafrines H-N were aspidosperma-type monomers. Their structures and absolute configurations were elucidated by a combination of NMR, MS, and ECD analyses. Voacafrines A-C were characterized by an acetonyl moiety at C-5', while voacafrine H possessed a methoxymethyl moiety at C-14 within aspidosperma-type alkaloids. The acetylcholinesterase (AChE) inhibitory activity and cytotoxicity of voacafrines A-N were evaluated. Voacafrines A-C and E-G were bisindole alkaloids that exhibited AChE inhibitory activity with IC50 values of 4.97-33.28 µM, while voacafrines I and J were monomers that showed cytotoxicity against several human cancer cell lines with IC50 values of 4.45-7.49 µM.

Therapeutic effects of Gambi-jung for the treatment of obesity.

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

The important herbal pair for the treatment of COVID-19 and its possible mechanisms.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19, and then analyze the active components and potential mechanisms of this herbal pair. METHODS: We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach, and analyzed the potential mechanisms against COVID-19. Finally, the main active compounds in the herbal pair were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) 3CLpro and angiotensin converting enzyme II (ACE2) for further verification. RESULT: We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19. The results showed that the combination of Amygdalus Communis Vas (ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value, as well as high support degree, which can be used in almost all the stages of COVID-19, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1ß (IL-1ß), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA). The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The potential pathways mainly involved tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE have good affinity with SARS-COV-2 3CLpro and ACE2, which are consistent with the above analysis. CONCLUSIONS: There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19. AE might have therapeutic effects against COVID-19 by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, targets and pathways.

Triterpenoids from the stems and leaves of Schisandra incarnata.

Six undescribed triterpenoids, schincarins A‒F, categorized as the preschisanartane (schincarin A), 3,4-secocycloartane (schincarins B‒D), 3,4; 9,10-disecocycloartane (schincarin E), and 3,4-secolanostane (schincarin F) classes, along with twelve known analogues, were obtained from the stems and leaves of Schisandra incarnata Stapf. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configuration of schincarin A was corroborated by analysis of the experimental ECD spectrum, and single-crystal X-ray diffraction with Mo Kα irradiation. Schincarin A represented the first example of preschisanartane-type triterpenoid with two oxa-bridged hemiketals. Among the selected compounds which were evaluated for immunosuppressive activities, schincarin C and kadsudilactone A showed potential inhibition against ConA-induced T-cell proliferation with IC50 values of 5.83 and 6.32 µM, and LPS-induced B cell proliferation with IC50 values of 10.21 and 11.49 µM, respectively.

Cymbopogon citratus aqueous leaf extract attenuates neurobehavioral and biochemical changes induced by social defeat stress in mice.

Objective: Psychosocial stress has been implicated in the genesis of psychiatric disorders such as memory deficits, depression, anxiety and addiction. Aqueous leaf extract of Cymbopogon citratus (CYC) otherwise known as lemongrass tea has antidepressant, anxiolytic and anti-amnesic effects in rodents. This study was designed to evaluate if C. citratus could reverse the neurobehavioral and biochemical derangements induced by social defeat stress (SDS) in the resident/intruder paradigm. Methods: Intruder male mice were divided into five groups (n = 7): group 1 received saline (10 mL/kg, p.o.; non-stress control), group 2 also received saline (10 mL/kg, p.o.; SDS control) while groups 3-5 had C. citratus (50, 100 and 200 mg/kg, p.o.) daily for 14 d. The SDS was carried out 30 min after each treatment from day 7 to day 14 by exposing each intruder mouse in groups 2-5 to a 10 min confrontation in the home cage of an aggressive resident counterpart. The neurobehavioral features (spontaneous motor activity-SMA, anxiety, memory, social avoidance and depression were then evaluated. The concentrations of nitrite, malondialdehyde and glutathione as well as acetylcholinesterase activity in the brain tissues were also determined. Results: C. citratus (50, 100 and 200 mg/kg) attenuated hypolocomotion, heightened anxiety, depressive-like symptom, memory deficit and social avoidance induced by SDS. The altered levels of oxidative stress and acetyl-cholinesterase in SDS-mice were positively modulated by C. citratus. Conclusion: The results of this study suggest that C. citratus might mitigate psychosocial stress-induced neurologic diseases in susceptible individuals.