Cytotoxic withanolides from the leaves of Datura stramonium L.

Six novel withanolides, along with nine known related compounds were isolated from the leaves of Datura stramonium L. The structures and absolute configurations of the new withanolides were elucidated by employing various spectral techniques and comparing them with those previously reported in the literature. In addition, four withanlides demonstrated interesting cytotoxic activity on LN229 cells with IC50 <20 µM.

New chromones from the roots of Saposhnikovia divaricata (Turcz.) Schischk with anti-inflammatory activity.

Fifteen new chromones, sadivamones A-E (1-5), cimifugin monoacetate (6), sadivamones F-N (7-15), together with fifteen known chromones (16-30), were isolated from the ethyl acetate portions of 70% ethanol extract of Saposhnikovia divaricata (Turcz.) Schischk roots. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. Meanwhile, LPS induced RAW264.7 inflammatory cell model was used to determine the potential anti-inflammatory activity of all the isolated compounds in vitro. The results showed that compounds 2, 8, 12-13, 18, 20-22, 24, and 27 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. To determine the signaling pathways involved in the suppression of NO production by compounds 8, 12 and 13, we investigated ERK and c-Jun N-terminal protein kinase (JNK) expression by western blot analysis. Further mechanistic studies demonstrated that compounds 12 and 13 inhibited the phosphorylation of ERK and the activation of ERK and JNK signaling in RAW264.7 cells via MAPK signaling pathways. Taken together, compounds 12 and 13 may be valuable candidates for the treatment of inflammatory diseases.

UHPLC-Orbitrap-Fusion-TMS-Based Metabolomics Study of Phenylpropionamides in the Seed of Cannabis sativa L. against Alzheimer's Disease.

Phenylpropionamides in the seed of Cannabis sativa L. (PHS) have a protective effect on neuroinflammation and antioxidant activity. In this study, the UHPLC-Orbitrap-fusion-TMS-based metabolomics approach was used to analyze the serum samples and identify potential biomarkers in Streptozotocin (STZ) induced Alzheimer's disease (AD) rats. The results revealed that primary bile acid biosynthesis and taurine and hypotaurine metabolism were significantly correlated with STZ-induced AD rats. In addition, the key enzymes in these two pathways were verified at the protein level. The levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD), cysteamine (2-aminoethanethiol) dioxygenase (ADO), 7α-hydroxylase (CYP7A1), and sterol 12α-hydroxylase (CYP8B1) were the key enzymes affecting the two pathways in AD rats compared with the control group (CON). Furthermore, after a high-dose group of phenylpropionamides in the seed of Cannabis sativa L. (PHS-H) was administrated, the levels of CDO1, CSAD, CYP7A1, and CYP8B1 were all callback. These findings demonstrate for the first time that the anti-AD effect of PHS is associated with the regulation of primary bile acid biosynthesis and taurine and hypotaurine metabolism in STZ-induced AD rats.

Phenylpropanoids from Solanum capsicoides and their anti-inflammatory activity.

Two new phenylpropanoids, 4-O-(1''-O-cis-caffeoyl)-ß-glucopyran osyl-1-allyl-3-methoxy-benzene (1), 4'-O-(1''-O-cis-caffeoyl)-ß-glucopyranosyl-hydroxymegastigm-4-en-3-one (2), together with nine known compounds were obtained from the leaves of Solanum capsicoides. Their structures were elucidated based on spectroscopic methods, and comparing spectral data with those in literature. Meanwhile, their anti-inflammatory activities were evaluated on (LPS)-induced RAW 246.7 cells, and 1, 9, and 10 showed better inhibitory effects with IC50 values of 17.19 ± 1.12, 18.15 ± 0.47, and 19.8 ± 0.95 µM, respectively.

Acorus tatarinowii Schott: A Review of Its Botany, Traditional Uses, Phytochemistry, and Pharmacology.

Acorus tatarinowii Schott (A. tatarinowii) is a natural medicinal plant. It plays an indispensable role in the treatment of diseases by the empirical medicine system and has achieved remarkable curative effects. A. tatarinowii is often used to treat various diseases, such as depression, epilepsy, fever, dizziness, heartache, stomachache, etc. More than 160 compounds of different structural types have been identified in A. tatarinowii, including phenylpropanoids, terpenoids, lignans, flavonoids, alkaloids, amides, and organic acids. These bioactive ingredients make A. tatarinowii remarkable for its pharmacological effects, including antidepressant, antiepileptic, anticonvulsant, antianxiety, neuroprotective, antifatigue, and antifungal effects, improving Alzheimer's disease, and so on. It is noteworthy that A. tatarinowii has been widely used in the treatment of brain diseases and nervous system diseases and has achieved satisfactory therapeutic effects. This review focused on the research publications of A. tatarinowii and aimed to summarize the advances in the botany, traditional uses, phytochemistry, and pharmacology, which will provide a reference for further studies and applications of A. tatarinowii.

Cytotoxic Sesquiterpenoids from Atractylodes chinensis (DC.) Koidz.

Four new sesquiterpenoids named atrchiterpenes A-D (1-4), a new natural product (5), and twelve known compounds (6-17) were isolated from Atractylodes chinensis (DC.) Koidz. Compound 1 was a rare N-containing eudesmane-type sesquiterpenoid. Structure elucidation was performed by spectroscopic techniques, including 1D, 2D NMR spectra, and HR-ESI-MS. Compounds 6-11, 14, and 17 were reported from Atractylodes for the first time. All the isolated compounds were evaluated for cytotoxicity activity. Compound 16 showed moderate cytotoxicity against HepG2 cells with an IC50 value of 5.81±0.47.

Chemical Constituents of the Roots of Schisandra chinensis.

One new phenylpropanoid schineolignin D (1), one new sesquiterpene (-)-(7S,10S)-3,11,12,13-tetrahydroxycalamenene (2), one new quinic acid 4-(E)-O-coumaroylquinic acid ethyl ester (3), and seven known compounds 4-10 were separated from the roots of Schisandra chinensis. The chemical structures of all compounds were characterized by NMR spectroscopic experiments. All compounds were assessed for their neuroprotective effects on PC12 cell lines induced by H2 O2 . Compounds 1, 3-4, and 7 showed statistically significant neuroprotective activities with the negative control group at 12.5 µM.

Aromatic glycosides from the aerial part of Bupleurum chinense.

A new aromatic glycoside (1) and twelve (2-13) known aromatic glycosides were isolated from the n-butyl alcohol of the 70% EtOH extract of the aerial part of Bupleurum chinense. Among them, compounds 4-7, 9, 11-13 were isolated from Umbelliferae plants for the first time. Their structures were elucidated by NMR and MS spectroscopy, and the absolute configuration of compound 1 was elucidated by single-crystal X-ray diffraction. Compounds 6 and 10 showed moderate cytotoxic activities on MGC-803 cell lines with IC50 values of 8.63 ± 0.08 and 13.65 ± 1.73 µM, respectively.

A new ent-kaurane diterpenoid from the pericarps of Datura metel.

A new ent-kaurane diterpenoid, named kaurane daturoside A (1), was isolated from the 70%-EtOH extract of dried pericarps of Datura metel L., along with six known terpenoids, 16α,17-dihydroxy-ent-kauran-19-diglycoside (2), cyclosieversioside F (3), astragaloside II (4), ginsenoside Rg1 (5), astrojanoside A (6), celerioside E (7). The isolated structures were elucidated by means of spectroscopic analyses, and the compounds 2, 3, 7 were separated from Solanaceae for the first time. Meanwhile, among isolates, compounds 2 and 5 exhibited anti-inflammatory activities against LPS-activated RAW264.7 cells (IC50<11.00 µM).

Two new quinic acid derivatives from the leaves of Schisandra chinensis.

Two new (1-2) and three known quinic acid derivatives (3-5) were isolated from the leaves of Schisandra chinensis (Turcz) Baill. The structures of the compounds were determined by spectroscopic methods, especially the NMR techniques, and also by comparison with reported data in the literature. The cytotoxicity activities of these compounds were evaluated on human tumor cell lines LN229 and three of them showed a certain activity.

Inositol Derivatives with Anti-Inflammatory Activity from Leaves of Solanum capsicoides Allioni

Eight new inositol derivatives, solsurinositols A-H (1-8), were isolated from the 70% EtOH extract of the leaves of Solanum capsicoides Allioni. Careful isolation by silica gel column chromatography followed by preparative high-performance liquid chromatography (HPLC) allowed us to obtain analytically pure compounds 1-8. They shared the same relative stereochemistry on the ring but have different acyl groups attached to various hydroxyl groups. This was the first time that inositol derivatives have been isolated from this plant. The chemical structures of compounds 1-8 were characterized by extensive 1D nuclear magnetic resonance (NMR) and 2D NMR and mass analyses. Meanwhile, the in vitro anti-inflammatory activity of all compounds was determined using lipopolysaccharide (LPS)-induced BV2 microglia, and among the isolates, compounds 5 (IC50 = 11.21 ± 0.14 µM) and 7 (IC50 = 14.5 ± 1.22 µM) were shown to have potential anti-inflammatory activity.

[Study on drug properties of Arisaematis Rhizoma and Arisaema Cum Bile based on substance and energy metabolism in normal and cold/heat syndrome model rats].

This paper clarified the scientific connotation of the changes in cold and heat properties of Arisaematis Rhizoma and Arisaema Cum Bile through investigating the changes of substance and energy metabolism after drug intervention in the rats with normal and cold/heat syndrome, so as to improve the method of evaluating the drug properties of Chinese medicine. After one week of adaptive feeding, healthy male SD rats were randomly divided into three parts: normal rats, heat syndrome rat models, and cold syndrome rat models. Through ice water bath and oral euthyrox(120 µg·kg~(-1)), the models of cold syndrome and heat syndrome were induced, respectively. The models were made at 9:00 am. and administrated by gavage at 3:00 pm. every day. All administration groups were administrated with Arisaematis Rhizoma and Arisaema Cum Bile decoction, respectively, and the blank group was given the same dose of normal saline. After continuous administration for 15 d, the rats were anesthetized by chloral hydrate, blood was taken from abdominal aorta, and the hearts and livers were removed and stored at-80 ℃. The changes in the body weight and anal temperature of rats during administration were detected, and the liver coefficient of rats was detected after removing the liver. Enzyme-linked immunosorbent assay(ELISA) was adopted to detect the expression level of the indexes related to substance and energy metabolism in liver and heart of rat, and Western blot was used to detect the expression of key proteins in AMPK/mTOR signaling pathway for further verification. The results showed that Arisaematis Rhizoma enhanced the expression level of enzymes related to substance and energy metabolism in the normal and cold and heat syndrome rat models, and increased anal temperature, which exhibited warm(hot) drug property. Arisaema Cum Bile inhibited the level of substance and energy metabolism in rats, and reduced anal temperature, which showed cold(cool) drug property. Chinese Pharmacopoeia has recorded "Arisaematis Rhizoma has warm property and Arisaema Cum Bile has cool property", which is consistent with the phenomenon in this study. Therefore, it is feasible to evaluate the drug properties of Chinese medicine based on the substance and energy metabolism of normal and cold/heat syndrome model rats, which completes the method of evaluating drug properties of Chinese medicine.

Ecdysteroids from the Aerial Parts of Paris verticillata.

Two new ecdysteroids 14-epi-polypodine B (1) and 22-oxo-hydroxyecdysterone (2), along with nine known compounds, polypodine B (3), viticosterone E (4), 20-hdroxyecdysone-2-acetate (5), 22-oxo-20-hydroxyecdysone (6), 5-hydroxyecdysone (7), pinnatasterone (8), 3-epi-20-hydroxyecdysone (9), ecdysterone (10) and stachysterone B (11), were isolated from the aerial parts of Paris verticillata. The structures of all compounds were elucidated by extensive spectroscopic analysis, quantum chemical calculations and ANN-PRA/DP4+ probability analysis. Among them, the absolute configuration of compound 1 and 2 was unambiguous determined by ECD. Also, the isolated compounds were assessed for their cytotoxic activities. Compounds 2, 3 and 7 exhibited significant cytotoxic activities against PC12, LN299 and SMCC7721 cells.

Discovery of Active Ingredients Targeted TREM2 by SPR Biosensor-UPLC/MS Recognition System, and Investigating the Mechanism of Anti-Neuroinflammatory Activity on the Lignin-Amides from Datura metel Seeds.

As a new target protein for Alzheimer's disease (AD), the triggering receptor expressed on myeloid Cells 2 (TREM2) was expressed on the surface of microglia, which was shown to regulate neuroinflammation, be associated with a variety of neuropathologic, and regarded as a potential indicator for monitoring AD. In this study, a novel recognition system based on surface plasmon resonance (SPR) for the TREM2 target spot was established coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-MS), in order to screen the active ingredients targeting TREM2 from Datura metel seeds. The results showed that four lignan-amides were discovered as candidate compounds by SPR biosensor-UPLC/MS recognition analysis. According to the guidance of the active ingredients discovered by the system, the lignin-amides from Datura metel seeds (LDS) were preliminarily identified as containing 27 lignan-amides, which were enriched compositions by the HP-20 of Datura metel seeds. Meanwhile, the anti-inflammatory activity of LDS was evaluated in BV2 microglia induced by LPS. Our experimental results demonstrated that LDS could reduce NO release in LPS-treated BV2 microglia cells and significantly reduce the expression of the proteins of inducible Nitric Oxide Synthase (iNOS), cyclooxygenase 2 (COX-2), microtubule-associated protein tau (Tau), and ionized calcium-binding adapter molecule 1 (IBA-1). Accordingly, LDS might increase the expression of TREM2/DNAX-activating protein of 12 kDa (DAP12) and suppress the Toll-like receptor SX4 (TLR4) pathway and Recombinant NLR Family, Pyrin Domain Containing Protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1) inflammasome expression by LDS in LPS-induced BV2 microglial cells. Then, the inhibitory release of inflammatory factors Interleukin 1 beta (IL-1ß), Interleukin 6 (IL-6), and Tumor necrosis factor-alpha (TNFα) inflammatory cytokines were detected to inhibit neuroinflammatory responses. The present results propose that LDS has potential as an anti-neuroinflammatory agent against microglia-mediated neuroinflammatory disorders.

A New Alkaloid from the Aerial Parts of Bupleurum chinense DC.

A new isoalloxazine alkaloid, named bupleurine A (1), along with five known compounds (2-6), were isolated from the aerial parts of Bupleurum chinense DC. The structure elucidation of the new alkaloid (1) was employed by combining NMR and HR-MS data with comparison of reference in the literature. Five known compounds (2-6) were isolated from Bupleurum genus for the first time. Additionally, their antiproliferative activities on HeLa cells were evaluated by MTT assay and IC50 of compounds 1 and 4-6 were below 10 µm after treatment for 24 h.

Lignans and Terpenoids from the Leaves of Schisandra chinensis.

Fifteen constituents, including one new lignan (schisandroside E) and one new terpenoid (schisandenoid A) as well as nine known lignans and four known terpenoids, were isolated from Schisandra chinensis leaves. The structures of schisandroside E and schisandenoid A were established by entirely meticulous spectroscopic analysis (NMR, MS, CD, IR and UV). All compounds were tested for cytotoxicity against MGC-803, Caco-2 and Ishikawa cell lines. Some compounds showed strong cytotoxicity against these three cancer cell lines with IC50 <1 µm.

Steroids from the seeds of Datura metel.

Two new steroids meteloside F (1) and meteloside G (2), together with six known ones (3-8), were isolated and identified from the seeds of Datura metel L. The chemical constituents were isolated by silica gel, ODS chromatogram columns. and preparative HPLC. The structures of these compounds were established by one- and two-dimensional NMR spectra and HR-ESI-MS. The compounds exhibited inhibition on the nitric oxide release of lipopolysaccharide-induced RAW 264.7 cells with IC50 values from 30.2 to 44.8 µM. [Formula: see text].

UPLC-MS/MS Identification and Quantification of Withanolides from Six Parts of the Medicinal Plant Datura Metel L.

Withanolides from six parts (flower, leaf, stem, root, seed, and peel) of Datura metel L. (D metel L.) obtained from ten production areas in China were identified and quantified by UPLC-MS/MS. A total of 85 withanolides were characterized for the first time using the UPLC-Q-TOF-MS/MS system. Additionally, a simultaneous, rapid and accurate measurement method was developed for the determination of 22 bioactive withanolides from ten production areas with the UPLC-Q-TRAP-MS/MS system. The results show the total withanolide content is highest in the leaves (155640.0 ng/g) and lowest in the roots (14839.8 ng/g). Compared with other production areas, the total content of plants from Dujiangyan was the highest at 82013.9 ng/g (value range of ten areas: 82013.9-42278.5 ng/g). The results also show significant differences in the distribution of withanolides in the different plant parts, as well as across different production areas. This is a breakthrough report providing a simultaneous qualitative and quantitative analysis of 22 withanolides in D. metel L. It could be the basis for the more rational use of various parts of D. metel L., and the expansion of medicinal resources. This work also lays a solid foundation for research on the quality control of D. metel L.

Melongenaterpenes A-L, Vetispirane-Type Sesquiterpenoids from the Roots of Solanum melongena.

Melongenaterpenes A-L (1-12), 12 new sesquiterpenoids with rare spiro[4.5]decane skeletons, were isolated from the roots of Solanum melongena. Their 2D structures and relative configurations were determined based on NMR and HRESIMS data. The absolute configuration of melongenaterpene A (1) was defined by X-ray crystallographic analysis. The absolute configurations of the remaining compounds were determined by comparison of their NMR data with 1 and consideration of the biosynthetic pathway. This is the first report of the crystal structure of a vetispirane-type sesquiterpenoid. None of the compounds exhibited cytotoxic activity against the three human cancer cell lines HepG2, HeLa, and MCF-7.

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8-MyD88-NF-κB-NLRP3 Inflammasome Pathway.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. METHODS: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7- myeloid differentiation primary response gene 88-nuclear Factor-κB-nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8-MyD88-NF-κB-NLRP3) inflammasome pathway. RESULTS: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1ß, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1ß. CONCLUSION: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8-MyD88-NF-κb-NLRP3 inflammasome pathway.