Five new eremophilane-type sesquiterpenes from the fresh roots of Rehmannia glutinosa.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi.

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Chemical constituents from stipes of Lentinus edodes and their protective effects against Aß25-35-induced N9 microglia cells injury.

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Dimeric diarylheptanoids with anti-inflammatory activity from Zingiber officinale.

Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4-8), together with one known cyclic diarylheptanoid (1) were isolated from Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1-8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.7 cells in a dose-dependent manner.

Five new biflavonoids with acetylcholinesterase inhibitory activity from Diphylleia sinensis.

Five new biflavonoids, diphybiflavonoids A - E (1-5), were isolated from the roots and rhizomes of Diphylleia sinensis. Their structures were elucidated by extensive spectroscopic data, including UV, IR, HR-ESI-MS and 2D NMR. Their absolute configurations were determined by ECD spectra. All isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activity. Compounds 1-4 exhibited the potent AChE inhibitory activities with IC50 values of 1.62, 2.10, 2.08, and 5.15 µM, respectively. The preliminary structure-activity relationship study indicated that the connection mode (C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''') of biflavonoid subunits, and 3-hydroxy group of flavonol subunit were important structural factors for AChE inhibitory activity. Biflavonoids, containing a C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''' linkage, can be a potentially useful platform for development of cholinesterase inhibitors.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

P-coumaric acid ameliorates Aß25-35-induced brain damage in mice by modulating gut microbiota and serum metabolites.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aß25-35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aß25-35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aß25-35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aß25-35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aß25-35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

[Effect of aqueous extract of Corni Fructus on Aß_(25-35)-induced brain injury and neuroinflammation in mice with Alzheimer's disease].

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on ß-amyloid protein 25-35(Aß_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aß_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of ß-amyloid protein 1-42(Aß_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aß_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol with ß-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aß_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aß_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aß_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aß_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aß_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

Unusual acetylated flavonol glucuronides, oxyphyllvonides A-H with renoprotective activities from the fruits of Alpinae oxyphylla.

As a widely consumed spice and Traditional Chinese Medicine, Alpinae oxyphylla has been used to treat conditions such as diarrhea, ulcers, dementia, and enuresis. Fruits of A. oxyphylla were phytochemically studied and the bioactive constituents against renal fibrosis were identified. Eight previously undescribed acetylated flavonol glucuronides named oxyphyllvonides A-H (1-7 and 10), two known acetylated flavonol glucuronides (8 and 9), together with seven known flavone glycosides (11-17) were isolated from the fruits of A. oxyphylla. Among them, flavonol glucuronides were discovered in Zingiberaceae for the first time. The planar structures of 1-7 and 10 were determined using HRESIMS and extensive spectroscopic techniques (UV, IR, 1D-NMR, and 2D-NMR). The absolute configurations of the sugar moiety in these compounds were determined by using LC-MS analysis of acid-hydrolyzed derivatized monosaccharides. Biological evaluation showed that 7-10, 13, 14, 16 and 17 inhibit renal fibrosis in TGF-ß1-induced kidney proximal tubular cells. In addition, 7, 8 and 14 were superior to nootkatone in inhibiting Fibronectin expression. The finding has significant relevance to our ongoing research on the anti-renal fibrosis activity of A. oxyphylla.

Diarylpentanoids and phenylpropanoids from the roots of Anthriscus sylvestris (L.) Hoffm.

Three pairs of undescribed diarylpentanoid enantiomers (1-3) and five undescribed phenylpropanoids (4-8), along with seven known compounds, were isolated from the roots of Anthriscus sylvestris. The structures of compounds (1-8) were determined by analysis of their 1D and 2D NMR spectra, HRESIMS, and electronic circular dichroism. In addition, the inhibitory activities against hypoxia-stimulated pulmonary arterial smooth muscle cells abnormal proliferation were evaluated by MTT assay. The mRNA expression levels of Bcl-2, BAX, Caspase3, and IL-6 were detected by quantitative real-time PCR. The results showed that compounds (-)-1, (+)-1, (-)-2, (+)-3, 4, 8-10, 14, and 15 inhibited the abnormal proliferation of PASMCs by regulating the levels of apoptosis and inflammatory factors.

Salviamilthone A-O, diterpenoid quinones from Salvia miltiorrhiza.

Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 µM) significantly increased cell viability and decreased the expression of IL-1ß in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.

Coptis chinensis-Induced Changes in Metabolomics and Gut Microbiota in Rats.

Rhizoma coptidis (CR) is traditionally used for treating gastrointestinal diseases. Wine-processed CR (wCR), zingiber-processed CR (zCR), and evodia-processed CR (eCR) are its major processed products. However, the related study of their specific mechanisms is very limited, and they need to be further clarified. The aim of this study is to compare the intervening mechanism of wCR/zCR/eCR on rats via faecal metabolomics and 16S rDNA gene sequencing analysis. First, faecal samples were collected from the control and CR/wCR/zCR/eCR groups. Then, a metabolomics analysis was performed using UHPLC-Q/TOF-MS to obtain the metabolic profile and significantly altered metabolites. The 16S rDNA gene sequencing analysis was carried out to analyze the composition of gut microbiota and screen out the significantly altered microbiota at the genus level. Finally, a pathway enrichment analysis of the significantly altered metabolites via the KEGG database and a functional prediction of relevant gut microbes based on PICRUSt2 software were performed in combination. Together with the correlation analysis between metabolites and gut microbiota, the potential intervening mechanism of wCR/zCR/eCR was explored. The results suggested that wCR played a good role in maintaining immune homeostasis, promoting glycolysis, and reducing cholesterol; zCR had a better effect on protecting the integrity of the intestinal mucus barrier, preventing gastric ulcers, and reducing body cholesterol; eCR was good at protecting the integrity of the intestinal mucus barrier and promoting glycolysis. This study scientifically elucidated the intervening mechanism of wCR/zCR/eCR from the perspective of faecal metabolites and gut microbiota, providing a new insight into the processing mechanism research of Chinese herbs.

Lanostane triterpenoids with anti-proliferative and anti-inflammatory activities from medicinal mushroom Ganoderma lingzhi.

Eight previously undescribed lanostane triterpenoids and nine known ones were identified from the fruiting bodies of Ganoderma lingzhi S.H. Wu, Y. Cao & Y.C. Dai. Their structures were determined based on spectroscopic data and quantum chemical calculations. Structurally, ganoderane GL-1, featuring a hydrogenated tetramethyls-phenanthraquinone, represents the first example in lanostane nor-triterpenoid group. Biologically, ganoderanes GL-2 and GL-3, distinguished by the presence of a rare "1,11-epoxy" moiety, exhibited significant inhibition against nitric oxide production induced by lipopolysaccharide in RAW264.7 macrophage cells, while ganoderanes GL-4 and GL-8 exhibited bifunctional activities of anti-proliferation and anti-inflammation.

Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities.

A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against α-glucosidase with IC50 of 1.11-33.53 µM, 5-150 times stronger than acarbose (IC50 = 169.78 µM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09-44.26 µM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 value of 47.13 µM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.

Pyrrole alkaloids from the fruiting bodies of edible mushroom Lentinula edodes.

Nine pyrrole alkaloid derivatives, including four new ones (1-4), were isolated from the wild mushroom Lentinula edodes for the first time. Their chemical structures were determined using UV-Vis spectroscopy, IR spectroscopy, MS, NMR spectroscopy, and single-crystal X-ray diffraction techniques. Compound 1, a previously unreported bicylo-pyrrole aldehyde homologue, was found to be a major component, approximately 8.2 µg g -1 in the dry powder of L. edodes. Compound 1 showed cytotoxicity against SMMC-772 (IC50 15.8 µM) without any cytotoxic effect on LO2, a normal hepatic cell line; compounds 1 and 2 displayed weak immunosuppressive activities by inhibiting the proliferation of induced T cells; compound 3 showed inhibition activity on the proliferation of HaCaT cell line (IC50 25.4 µM) and weak antioxidant activity at a concentration of 50 µM.

2-phenylacetamide Separated from the seed of Lepidium apetalum Willd. inhibited renal fibrosis via MAPK pathway mediated RAAS and oxidative stress in SHR Rats.

BACKGROUND: Renal fibrosis with Renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress are one of the major complications in hypertension. 2-phenylacetamide (PA), a major active component of Lepidium apetalum Willd. (L.A), has numerous pharmacological effects. Its analogues have the effect of anti-renal fibrosis and alleviating renal injury. This study aims to explore the underlying mechanism of PA for regulating the renal fibrosis in SHR based on the MAPK pathway mediated RAAS and oxidative stress. METHODS: The SHR rats were used as the hypertension model, and the WKY rats were used as the control group. The blood pressure (BP), urine volume were detected every week. After PA treatment for 4 weeks, the levels of RAAS, inflammation and cytokines were measured by Enzyme-Linked Immunosorbnent Assay (ELISA). Hematoxylin-Eosin staining (HE), Masson and Immunohistochemistry (IHC) were used to observe the renal pathology, collagen deposition and fibrosis. Western blot was used to examine the MAPK pathway in renal. Finally, the SB203580 (p38 MAPK inhibitor) antagonism assay in the high NaCl-induced NRK52e cells was used, together with In-Cell Western (ICW), Flow Cytometry (FCM), High Content Screening (HCS) and ELISA to confirm the potential pharmacological mechanism. RESULTS: PA reduced the BP, RAAS, inflammation and cytokines, promoted the urine, and relieved renal pathological injury and collagen deposition, repaired renal fibrosis, decreased the expression of NADPH Oxidase 4 (NOX4), transforming growth factor-ß (TGF-ß), SMAD3 and MAPK signaling pathway in SHR rats. Meanwhile,,the role of PA could be blocked by p38 antagonist SB203580 effectively in the high NaCl-induced NRK52e cells. Moreover, molecular docking indicated that PA occupied the ligand binding sites of p38 MAPK. CONCLUSION: PA inhibited renal fibrosis via MAPK signalling pathway mediated RAAS and oxidative stress in SHR Rats.

Naringenin and apigenin ameliorates corticosterone-induced depressive behaviors.

Background: Depression is a common kind of mental illness, and it becomes the main health burden in the world. Purpose: The aim of this study was to investigate the antidepressant effects of naringin and apigenin isolated from Chrysanthemum morifolium Ramatis. Methods: Firstly, 20 mg/kg corticosterone (CORT) was injected into mice to establish an in vivo model of depression. After treated with different dosages of naringenin and apigenin for 3 weeks, the mice underwent a series of behavioral experiments. Following this, all mice were sacrificed and biochemical analyses were performed. Subsequently, CORT (500 µM) induced PC12 cells was used as an in vitro model of depression, and lipopolysaccharide (LPS) (1 µg ml-1) induced N9 microglia cells was used as an in vitro model of neuroinflammation in N9 microglia cells, to investigate the neuroprotective mechanisms of naringenin and apigenin. Results: Results showed that the naringenin and apigenin treatment ameliorated CORT-induced sucrose preference decrease and immobility time increase, elevated the 5-hydroxytryptamine(5-HT), dopamine (DA) and norepinephrine (NE) levels, and enhanced the cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) protein expressions in the hippocampus. The results showed that the naringenin and apigenin treatment improved the PC-12 cell viability through reducing apoptosis rate induced by CORT. Furthermore, naringenin and apigenin were able to inhibit the activation of N9 cells after LPS induction, and shift microglia from proinflammatory M1 microglia toward anti-inflammatory M2 microglia, as evidenced by the decreased ratio of M1 type microglia marker CD86 and M2 type microglia marker CD86. Conclusion: These results suggested that naringenin and apigenin may improve depressive behaviors through promoting BDNF and inhibiting neuroinflammation and neuronal apoptosis.

Tingli Dazao Xiefei Decoction ameliorates asthma in vivo and in vitro from lung to intestine by modifying NO-CO metabolic disorder mediated inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a chronic airway inflammatory disease. Current treatment of mainstream medications has significant side effects. There is growing evidence that the refractoriness of asthma is closely related to common changes in the lung and intestine. The lungs and intestines, as sites of frequent gas exchange in the body, are widely populated with gas signaling molecules NO and CO, which constitute NO-CO metabolism and may be relevant to the pathogenesis of asthma in the lung and intestine. The Chinese herbal formula Tingli Dazao Xiefei Decoction (TD) is commonly used in clinical practice to treat asthma with good efficacy, but there are few systematic evaluations of the efficacy of asthma on NO-CO metabolism, and the mode of action of its improving effect on the lung and intestine is unclear. AIM OF THE STUDY: To investigate the effect of TD on the lung and intestine of asthmatic rats based on NO-CO metabolism. MATERIALS AND METHODS: In vivo, we established a rat asthma model by intraperitoneal injection of sensitizing solution with OVA atomization, followed by intervention by gavage administration of TD. We simultaneously examined alterations in basal function, pathology, NO-CO metabolism, inflammation and immune cell homeostasis in the lungs and intestines of asthmatic rats, and detected changes in intestinal flora by macrogenome sequencing technology, with a view to multi-angle evaluation of the treatment effects of TD on asthmatic rats. In vitro, lung cells BEAS-2B and intestinal cells NCM-460 were used to establish a model of lung injury causing intestinal injury using LPS and co-culture chambers, and lung cells or intestinal cells TD-containing serum was administered to intervene. Changes in inflammatory, NO-CO metabolism-related, cell barrier-related and oxidative stress indicators were measured in lung cells and intestinal cells to evaluate TD on intestinal injury by way of amelioration and in-depth mechanism. RESULTS: In vivo, our results showed significant basal functional impairment in the lung and intestine of asthmatic rats, and an inflammatory response, immune cell imbalance and intestinal flora disturbance elicited by NO-CO metabolic disorders were observed (P < 0.05 or 0.01). The administration of TD was shown to deliver a multidimensional amelioration of the impairment induced by NO-CO metabolic disorders (P < 0.05 or 0.01). In vitro, the results showed that LPS-induced lung cells BEAS-2B injury could cause NO-CO metabolic disorder-induced inflammatory response, cell permeability damage and oxidative stress damage in intestinal cells NCM-460 (P < 0.01). The ameliorative effect on intestinal cells NCM-460 could only be exerted when TD-containing serum interfered with lung cells BEAS-2B (P < 0.01), suggesting that the intestinal ameliorative effect of TD may be exerted indirectly through the lung. CONCLUSION: TD can ameliorate NO-CO metabolism in the lung and thus achieve the indirectly amelioration of NO-CO metabolism in the intestine, ultimately achieving co-regulation of lung and intestinal inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders in asthma in vivo and in vitro. Targeting lung and intestinal NO-CO metabolic disorders in asthma may be a new therapeutic idea and strategy for asthma.

[Alkaloids from fruit of Lycium chinense var. potaninii].

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 µmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.