Traditional Chinese medicine in regulating macrophage polarization in immune response of inflammatory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous studies have demonstrated that various traditional Chinese medicines (TCMs) exhibit potent anti-inflammatory effects against inflammatory diseases mediated through macrophage polarization and metabolic reprogramming. AIM OF THE STUDY: The objective of this review was to assess and consolidate the current understanding regarding the pathogenic mechanisms governing macrophage polarization in the context of regulating inflammatory diseases. We also summarize the mechanism action of various TCMs on the regulation of macrophage polarization, which may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization. MATERIALS AND METHODS: We conducted a comprehensive review of recently published articles, utilizing keywords such as "macrophage polarization" and "traditional Chinese medicines" in combination with "inflammation," as well as "macrophage polarization" and "inflammation" in conjunction with "natural products," and similar combinations, to search within PubMed and Google Scholar databases. RESULTS: A total of 113 kinds of TCMs (including 62 components of TCMs, 27 TCMs as well as various types of extracts of TCMs and 24 Chinese prescriptions) was reported to exert anti-inflammatory effects through the regulation of key pathways of macrophage polarization and metabolic reprogramming. CONCLUSIONS: In this review, we have analyzed studies concerning the involvement of macrophage polarization and metabolic reprogramming in inflammation therapy. TCMs has great advantages in regulating macrophage polarization in treating inflammatory diseases due to its multi-pathway and multi-target pharmacological action. This review may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization.

Abelmoschus manihot (L.) medik. seeds alleviate rheumatoid arthritis by modulating JAK2/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Abelmoschus manihot (L.) Medik. Seeds (AMS, སོ་མ་ར་ཛ།), a Tibetan classical herbal in China, are rich in flavonoids and phenolic glycosides compounds, such as quercetin and its derivatives. Moreover, it has been found to possess anti-rheumatoid arthritis (RA) effects. Nonetheless, its anti-RA mechanism is yet unknown. AIM OF THE STUDY: This research aimed to examine the active ingredients of AMS as well as potential pharmacological mechanisms in AMS on RA. MATERIALS AND METHODS: The ultra-performance liquid chromatography-electrospray ionization-tandem multistage mass spectrometry (UPLC-ESI-IT-MSn) technique was used to determine the primary chemical components of AMS that were responsible for the therapeutic effects on RA. In addition, 36 male Wistar rats weighing between 200 and 220 g were classified at random into six groups [normal control group, collagen-induced arthritis (CIA) group, methotrexate group (positive control, 1.05 mg/kg), AMS group (157.5 mg/kg, 315 mg/kg, 630 mg/kg)]. CIA rats were given AMS extract by intragastric administration for 28 days, and their ankles were photographed to observe the degree of swelling. Further, the arthritis score, paws swelling, and body weight changes of CIA rats were determined to observe whether AMS has any effect on RA, and synovial and cartilage tissue injuries were identified by histopathology. Besides, the levels of IL-10, TNF-α, IL-1ß, INF-γ, etc. in serum were estimated by ELISA. Western blot experiments were implemented to identify the expression levels of protein involved in the JAK2/STAT3 signaling pathway in the CIA rats' synovial tissues. Moreover, the mechanisms and targets of active ingredient therapy of AMS for RA were predicted using network pharmacology and then verified using molecular docking. RESULT: In the present study, 12 compounds were detected by UPLC-ESI-IT-MSn, such as quercetin and its derivative which could be potential active ingredients that contribute to the anti-RA properties of AMS. Our in vivo studies on CIA rats revealed that an AMS-H dose of 630 mg/kg significantly improved joint damage while decreasing the arthritic index and paw swelling. Furthermore, AMS inhibited the INF-γ, IL-6, IL-17, IL-1ß, and TNF-α, levels while upregulating the expression of anti-inflammatory cytokines IL-10 and IL-4 in serum. Besides, AMS inhibited the protein Bcl-2/Bax, STAT3, and JAK2 levels, and promoted the expression of Caspase3, SOCS1, and SOCS3 in the JAK2/STAT3 pathway. Additionally, the JAK/STAT signaling pathway was found to perform a remarkable function in the AMS therapy of RA as evidenced by enrichment in GO terms and KEGG pathways. Meanwhile, data from molecular docking experiments indicated that the core targets of PIK3CA, JAK2, and SRC bound stably to the active ingredients of mimuone, 4'-methoxy-bavachromanol, and quercetin. CONCLUSION: According to these findings, the AMS could improve joint inflammation in CIA rats, and its underlying mechanism could be linked to the regulation of the JAK2/STAT3 pathway. Therefore, AMS might become a promising agent for alleviating inflammation in RA patients.

Cytotoxic tetronic acid derivatives from the mangrove endophytic fungus Hypomontagnella monticulosa YX702.

Three new tetronic acid derivatives, nodulisporacid A ethyl ester (3), isosporothric acid methyl ester (4), and (R)-3-(methoxycarbonyl)-2-methyleneundecanoic acid (5) were isolated from mangrove endophytic fungus Hypomontagnella monticulosa YX702, together with three known analogues nodulisporacid A (1), nodulisporacid A methyl ester (2), and dihydrosporothriolide (6). The structures of these new compounds were elucidated by analysis of NMR and HR-ESI-MS spectroscopic data. In addition, the absolute configuration of nodulisporacid A (1) was confirmed by single-crystal X-ray diffraction for the first time. Subsequently, the absolute configuration of compounds 2 and 3 were determined by chemical derivatization of nodulisporacid A (1). The absolute configuration of compound 4 and 5 were established by TDDFT ECD calculations. Compounds 1 and 2 exhibited cytotoxic activities against A549 and Hela cancer cell lines with the IC50 values between 5.64 and 8.14 µM.

Tibetan medicine Qi-Sai-Er-Sang-Dang-Song Decoction inhibits TNF-α-induced rheumatoid arthritis in human fibroblast-like synoviocytes via regulating NOTCH1/NF-κB/NLRP3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qi-Sai-Er-Sang-Dang-Song Decoction (QSD, ཆུ་སེར་སེང་ལྡེང་སུམ་ཐང་།), a Tibetan classical herbal formula, is commonly used in Tibetan hospital preparation for the treatment of rheumatoid arthritis (RA). Its efficacy is to relieve inflammation, dispel cold, remove dampness, and alleviate pain. However, its anti-RA mechanism is still unclear. AIM OF THE STUDY: This study aimed to investigate the effect of QSD on rheumatoid arthritis and explore its anti-inflammatory mechanism against human fibroblast-like synoviocytes (HFLSs) by regulating the notch family of receptors (NOTCH1)/Nuclear factor-κB (NF-κB)/nucleotide-binding (NLRP3) pathway. MATERIALS AND METHODS: We used ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS) to identify the chemical composition of QSD. Then, HFLSs were exposed to drug-containing serum. The effect of QSD drug-containing serum on HFLS viability was detected using the cell counting kit-8 (CCK-8) assay. Next, we explored the anti-inflammatory effect of QSD using enzyme-linked immunosorbent assay (ELISA) for inflammatory factors, such as interleukin-18 (IL-18), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). The expression of NOTCH-related proteins, a member of the NOTCH1, Cleaved NOTCH1, hairy and enhancer of split-1 (HES-1), NF-κB p65, NF-κB pp65, NLRP3, and delta-like 1 (DLL-1), was examined using western blotting. Furthermore, the relative mRNA expression levels of NOTCH1, NF-κB p65, NLRP3, DLL-1, and HES-1 were detected using real-time quantitative (RT-qPCR). To explore the mechanism underlying the anti-RA effect of QSD, we the used the NOTCH signaling pathway inhibitor LY411575 and transfection with a NOTCH1 siRNA. In addition, we employed immunofluorescence to determine the expression of HES-1 and NF-κB p65 in vitro. RESULT: Our results revealed that QSD ameliorated inflammation in HFLSs. Compared with the model group, the QSD drug-containing serum group had obviously down-regulated levels of IL-18, IL-1ß, and IL-6. Consistently, the CCK-8 results showed that the QSD drug-containing serum had no obvious toxicity towards HFLSs. Moreover, both LY411575 and siNOTCH1, QSD could reduce NOTCH1, NLRP3, and HES-1 protein expression levels, and LY411575 could significantly inhibit the expression levels of NF-κB p65, NF-κB pp65, and Cleaved NOTCH1 (p < 0.05). siNOTCH1 could also suppress the expression of DLL-1. The RT-qPCR results indicated that QSD could downregulate the relative mRNA expression levels of NOTCH1, NF-κB p65, NLRP3, DLL-1, and HES-1 in HFLSs (p < 0.05). In the immunofluorescence experiment, the fluorescence intensities of HES-1 and NF-κB p65 in HFLSs were found to decrease after exposure to QSD drug-containing serum (p < 0.05). Ultimately, 44 chemical components were detected in QSD using UPLC-Q-TOF-MS. CONCLUSION: This study reveals that the QSD can markedly ameliorate inflammation induced by TNF-α on HFLS. The effect of QSD on HFLS may be exerted by inhibition of the NOTCH1/NF-κB/NLRP3 signaling pathway.

In vitro and in vivo exploration of the anti-atopic dermatitis mechanism of action of Tibetan medicine Qi-Sai-Er-Sang-Dang-Song decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan medicine Qi-Sai-Er-Sang-Dang-Song Decoction(QSD, ཆུ་སེར་སེང་ལྡེང་སུམ་ཐང་།)is a traditional Tibetan medical formulation with demonstrated clinical benefits in atopic dermatitis (AD). However, its potential mechanism and molecular targets remain to be elucidated. AIM OF THE STUDY: This study aims to explore the activity and mechanism of QSD on AD in multiple dimensions by combining in vitro and in vivo experiments with network pharmacology. MATERIALS AND METHODS: The AD effect of QSD was investigated by evaluating the levels of nitric oxide (NO) and interleukin-6 (IL-6) in the lipopolysaccharide (LPS) stimulated RAW264.7 cells. AD-like skin lesions in female BALB/c mice were induced by 2,4-dinitrochlorobenzene (DNCB). QSD or dexamethasone (positive control) were gavagely administered daily for 15 consecutive days. The body weight and skin lesion severity were recorded throughout the study. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis were used to illuminate the molecular targets associated with the anti-AD effects of QSD. Meanwhile, the ingredients of QSD in the blood were revealed and analyzed by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method. Network pharmacology was used to predict the targets and mechanism of active ingredient therapy for AD. In addition, the network pharmacology outcomes were further verified by molecular docking. RESULT: After treatment with QSD, the levels of NO and IL-6 were decreased in the cell supernatant. Herein, QSD markedly decreased the eosinophil and mast cells infiltration in the dorsal skin of the 2,4-dinitrochlorobenzene. Moreover, QSD reconstructed the epidermal barrier by increasing the content of collagen fibers and changing the arrangement of DNCB-treated mice. QSD not only inhibited the levels of tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) but also inhibited phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) proteins in the dorsal skin. Four active ingredients were identified through UPLC-Q-TOF/MS, including (-)-epicatechin, kaempferol-7-O-glucoside, cassiaside, and questin. After the network pharmacological analysis, six core targets of QSD closely related to AD were obtained, including TNF-α, IL-6, Caspase-3 (CASP3), Epidermal growth factor (EGFR), Peroxisome proliferator-activated receptor gamma (PPARG), and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1). Meanwhile, through Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, the Mitogen-activated protein kinase (MAPK) signaling pathway occupies an important position in the QSD treatment of AD. The molecular docking results showed that the six core targets are stable in binding to the four active ingredients as indicated by the molecular docking results. CONCLUSIONS: The anti-AD effect of QSD might be related to the reconstruction of the epidermal barrier and inhibition of inflammation, which regulated the MAPK pathway. Hence, it provided a promising idea for the study of Tibetan medicine prescriptions for the treatment of AD.

Development of a mass spectrometry-based metabolomics workflow for traceability of wild and cultivated Cordyceps sinensis.

Cordyceps sinensis, as an expensive traditional Chinese medicine and edible fungus mycelium, lacks an effective quality evaluation method, especially and cultivated Cordyceps sinensis. In this study, a feasible workflow method was developed for traceability evaluation of wild and cultivated Cordyceps sinensis, based on mass spectrometry-based metabolomics. Mass spectrometry data were firstly acquired from Cordyceps sinensis, samples by liquid chromatography-quadrupole and time of flight mass spectrometry. Characteristic mass spectrometry peaks were extracted by applying the MZmine. Then significant markers were obtained from Cordyceps sinensis samples by orthogonal partial least square discriminant analysis. Then, identification of significant markers were identified by MS-FINDER data analytics. The results showed that Changdu, the other four wild origins (Naqu, Xinghai, Yushu and Guoluo) and cultivated samples could be significantly distinguished. This identified significant markers of Cordyceps sinensis, including 174 special significant markers for the wild samples, 204 special significant markers for the cultivated samples and 87 share significant markers. Number of 87 shared significant markers were identified in the wild and cultivated Cordyceps sinensis, especially 28 confident significant compounds, such as adenosine, riboflavin, tyrosine, arginine and glutamine. These shared significant markers might support the quality control of multi-targets of Cordyceps sinensis, compared with a single target in the Chinese Pharmacopoeia. The special significant markers indicated that cultivated Cordyceps sinensis was different from the wild based on mass spectrometry-based metabolomics. In the comparison of chromatographic fingerprint technology, it was found that the established feasible workflow method was easy to acquire significant markers and traceability of Cordyceps sinensis. This feasible workflow method has great potential to be successful for comprehensive and traceability evaluation of the wild and cultivated Cordyceps sinensis.

Pivotal regulatory roles of traditional Chinese medicine in ischemic stroke via inhibition of NLRP3 inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have demonstrated the powerful neuroprotection abilities of multiple traditional Chinese medicines (TCMs) against NLRP3 inflammasome-mediated ischemic cerebral injury. These TCMs may be in the form of TCM prescriptions, Chinese herbal medicines and their extracts, and TCM monomers. AIM OF THE STUDY: This review aimed to analyze and summarize the existing knowledge on the assembly and activation of the NLRP3 inflammasome and its role in the pathogenesis of ischemic stroke (IS). We also summarized the mechanism of action of the various TCMs on the NLRP3 inflammasome, which may provide new insights for the management of IS. MATERIALS AND METHODS: We reviewed recently published articles by setting the keywords "NLRP3 inflammasome" and "traditional Chinese medicines" along with "ischemic stroke"; "NLRP3 inflammasome" and "ischemic stroke" along with "natural products" and so on in Pubmed and GeenMedical. RESULTS: According to recent studies, 16 TCM prescriptions (officially authorized products and clinically effective TCM prescriptions), 7 Chinese herbal extracts, and 29 TCM monomers show protective effects against IS through anti-inflammatory, anti-oxidative stress, anti-apoptotic, and anti-mitochondrial autophagy effects. CONCLUSIONS: In this review, we analyzed studies on the involvement of NLRP3 in IS therapy. Further, we comprehensively and systematically summarized the current knowledge to provide a reference for the further application of TCMs in the treatment of IS.

Huang-Lian-Jie-Du decoction attenuates cognitive dysfunction of rats with type 2 diabetes by regulating autophagy and NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du decoction (HLJDD) is a traditional Chinese formula that is efficacious in treating diabetes mellitus, Alzheimer's disease, and diabetic encephalopathy; the underlying mechanisms of HLJDD in diabetes-associated cognitive dysfunction remain unclear. AIM OF THE STUDY: This study investigated the neuroprotective effects of HLJDD on cognitive function, and the possible underlying mechanisms in type 2 diabetes mellitus (T2DM) in a rat model of cognitive impairment. MATERIALS AND METHODS: Twelve active ingredients in HLJDD were detected using high-performance liquid chromatography analysis. An animal model of cognitive dysfunction in T2DM was induced via a high-sugar and high-fat diet combined with a low dose of streptozotocin. Sprague-Dawley rats were randomly divided into six groups: control, T2DM, metformin (0.34 g/kg/day), and HLJDD groups (3, 1.5, and 0.75 g/kg/day). All treatments were intragastrically administrated for nine continuous weeks after the development of T2DM. Body weight, food and water intake, fasting blood glucose, insulin sensitivity, and blood lipid levels were measured. Spatial learning and memory of the rats were assessed using the Morris water maze test. Hematoxylin and eosin and Nissl staining were performed to evaluate neuronal morphology and vitality. Glutathione, malondialdehyde, and superoxide dismutase levels were measured to determine the level of oxidative stress in the hippocampus. Transmission electron microscopy was performed to observe the synaptic morphology and structure of hippocampal neurons. IL-1ß levels in the hippocampus and cerebrospinal fluid were determined. The protein expression of NLRP3, cleaved caspase-1, mature IL-1ß, ATG7, P62, LC3, and brain-derived neurotrophic factor (BDNF) was determined using western blotting and immunofluorescence analysis. RESULTS: HLJDD attenuated cognitive dysfunction in rats with T2DM as shown by the decreased escape latency, increased times crossing the platform and time spent in the target quadrant in the Morris water maze test (P < 0.05), improvement in hippocampal histopathological changes, and an elevated level of cell vitality. HLJDD treatment also reduced blood glucose and lipid levels, ameliorated oxidative stress, and downregulated IL-1ß expression in the hippocampus and cerebrospinal fluid (P < 0.05). Moreover, HLJDD enhanced BDNF, ATG7, and LC3 protein expression and significantly inhibited the expression of P62, NLRP3, cleaved caspase-1, and mature IL-1ß in the hippocampal CA1 region (P < 0.05). Immunofluorescence results further confirmed that the fluorescence intensity of NLRP3 and P62 in the hippocampus decreased after HLJDD intervention (P < 0.05). CONCLUSIONS: HLJDD ameliorated cognitive dysfunction in T2DM rats. The neuroprotective effect is exerted via the modulation of glucose and lipid metabolism, upregulation of autophagy, and inhibition of NLRP3 inflammasome signaling pathway.

Dengzhan Xixin injection derived from a traditional Chinese herb Erigeron breviscapus ameliorates cerebral ischemia/reperfusion injury in rats via modulation of mitophagy and mitochondrial apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan Xixin injection (DX), a preparation of extracts from traditional Chinese medicine Erigeron breviscapus (Vaniot) Hand.-Mazz., has been widely used in clinical treatment of cerebral ischemia sequelae in China for a long history. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The objective of this present study aimed to investigate the therapeutic effects of DX on cerebral ischemia/reperfusion (I/R) injury in a rat model. Meanwhile, its underlying molecular mechanisms on mitochondrial protection were further interpreted. MATERIALS AND METHODS: The major components of DX were detected by high-performance liquid chromatography analysis. The model of cerebral I/R injury was established by middle cerebral artery occlusion (MCAO) in SD rats. We firstly performed neurobehavioral score, the regional cerebral blood flow (rCBF) assay, and TTC, HE and Nissl staining for evaluating the effects of DX on I/R injury. And then, the cortical levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) were determined by commercial kits. Whereafter, real time-PCR and transmission electron microscopy were employed to investigate the relative copy number of mitochondrial DNA (mtDNA) and neuronal ultrastructure changes, respectively. Further, the potential interactions of major components in DX with mitophagy/apoptosis-related proteins were predicted by Schrodinger molecular docking. The expression of mitophagy-related proteins LC3, p62, TOM20, PINK1 and Parkin was estimated by western blot and immunofluorescence analyses. Furthermore, TUNEL staining and western blot were used to detect the apoptotic phenomenon and the protein expression of Bax, Bcl-2, Cytochrome c (Cyto-c) and cleaved Caspase-3. RESULTS: DX mainly contains scutellarin, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, caffeic acid and 5-O-caffeoylquinic acid. Compared with the model group, DX could remarkably relieve ischemia-provoked neurological deficit, rCBF deficiency and cerebral infarction. Pathological changes and neuronal loss in a MCAO model of rats were memorably ameliorated by DX administration. Meanwhile, DX reduced the surged ROS and MDA, while increased the level of SOD. Notably, DX treatment conversed the collapse of ATP and MMP, along with decreased in the relative copy number of mtDNA, contributing to the maintaining of mitochondrial ultrastructure via the increased number of autophagy lysosomes. The representative ingredients in DX had a potential bind with the active sites of mitophagy/apoptosis-related proteins. DX stimulated the protein expression of LC3, PINK1 and Parkin, while reduced the levels of p62 and TOM20. In addition, DX confined TUNEL-positive cell rate with the decreased expressions of Bax, Cyto-c and cleaved Caspase-3 as well as the increased Bcl-2 level. CONCLUSIONS: We demonstrated that the protection of DX against brain ischemia could attribute to alleviating mitochondrial damage by upregulating mitophagy and inhibiting mitochondria-mediated apoptosis.

Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata 'Chachi') under different harvesting and drying conditions.

BACKGROUND: The Citrus reticulata 'Chachi' pericarp (CRCP) is one cultivar of Citri Reticulatae Pericarpium (Chenpi), which is widely applied in medicine and food. To determine the potential value of CRCP harvested at different stages and subjected to different drying processes, the dynamic changes in the bioactive components were profiled and evaluated in this study. RESULTS: The contents of all non-volatile components, i.e. synephrine, limonin, phenolic acids and flavonoids, decreased with delayed harvest time. The volatiles thujene, α-pinene, ß-pinene, d-citronellol, d-citronellal, decanal, linalool, geraniol, l-cis-carveol, terpinen-4-ol, α-terpineol, carvacrol, perillaldehyde, methyl 2-(methylamino)benzoate and d-limonene were considered the characteristic components for distinguishing CRCP harvested at different stages. Phenolic acids, synephrine and limonin were stable at different drying temperatures; however, high-temperature drying at 60 °C induced a significant transformation in the flavonoids (especially polymethoxyflavones) and volatile substances in CRCP. CONCLUSIONS: The results suggested that most of the bioactive components declined with the growth of Citrus reticulata 'Chachi'. And it is believed that the fresh peel should be naturally sun-dried or dried at low temperature (30 or 45 °C) rather than at high temperature (60 °C) to prevent excessive loss of nutrients. © 2020 Society of Chemical Industry.

Identification of lipophilic components in Citri Reticulatae Pericarpium cultivars by supercritical CO2 fluid extraction with ultra-high-performance liquid chromatography-Q Exactive Orbitrap tandem mass spectrometry.

To systematically identify the lipophilic constituents of Citri Reticulatae Pericarpium from different cultivars, supercritical CO2 fluid extraction and ultra-high-performance liquid chromatography-Q Exactive Orbitrap tandem mass spectrometry were integrated for the component analysis of 18 batches of Citri Reticulatae Pericarpium from 12 cultivars for the first time. A total of 57 components from the supercritical CO2 fluid extracts were demonstrably or tentatively identified by the obtained parent peaks, fragment peaks, and retention times. In total, two flavonoids, six organic acids, nine coumarins, three aldehydes, seven esters, three terpenes, one limonoid, and five other compounds were detected for the first time; notably, coumarin components have not yet been reported in Citri Reticulatae Pericarpium. Furthermore, the extract constituents differed between cultivars. In particular, organic acids were more abundant in Citrus reticulata "Chachi" than in other cultivars, and pterostilbene was exclusively found in Citrus reticulata "Yichangju". The results showed that a greater variety of compounds in Citri Reticulatae Pericarpium could be extracted by supercritical CO2 fluid extraction and detected by ultra-high-performance liquid chromatography-Q Exactive Orbitrap tandem mass spectrometry. This study provides a more scientific basis for further analysis of the pharmacological activity and quality of Citri Reticulatae Pericarpium components from different cultivars.

Grincamycins I - K, Cytotoxic Angucycline Glycosides Derived from Marine-Derived Actinomycete Streptomyces lusitanus SCSIO LR32.

Three new angucycline glycosides, designated grincamycin I (1: ), J (2: ), and K (3: ), together with the known congener A-7884 (4: ), were isolated from marine-derived actinomycete Streptomyces lusitanus SCSIO LR32. The structures of the new compounds were elucidated by comprehensive spectral data analysis. Compounds 2: and 4: exhibited antitumor activity against human cancer cells MDA-MB-435, MDA-MB-231, NCI-H460, HCT-116 and HepG2, and human normal breast epithelial cell MCF10A with IC50 values ranging from 0.4 to 6.9 µM. In addition, A-7884 (4: ) demonstrated antimicrobial activity against Micrococcus luteus with an MIC value of 1.95 µg/mL.

Antimycobacterial activity of fusaric acid from a mangrove endophyte and its metal complexes.

Due to the increasing prevalence of multidrug-resistant Mycobacterium tuberculosis, there is an urgent need for new antituberculosis drugs that have novel mechanisms of action. As part of our ongoing search for antimycobacterial metabolites from mangrove endophytes, chemical analysis of the active extract of a strain of Fusarium sp. was performed, which led to the isolation of fusaric acid as the predominant constituent. A variety of metal complexes of fusaric acid were prepared. Antimycobacterial assays showed that Cadmium (II) and Copper (II) complexes exhibited potent inhibitory activity against the M. bovis BCG strain [minimum inhibitory concentration (MIC) = 4 µg/mL] and the M. tuberculosis H37Rv strain (MIC = 10 µg/mL), respectively. This is the first report of the antimycobacterial activity of the mangrove Fusarium metabolite and its coordinating metal complexes.