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Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1711-1728页

作者： Crystal Ngofi Zumbi Chun-Hsu Pan Hui-Yu Huang Chieh-Hsi Wu Program in Clinical drug Development from herbal Medicine College of PharmacyTaipei Medical UniversityTaipei 11031China Program in drug Discovery and Development Industry College of PharmacyTaipei Medical UniversityTaipei 11031China School of Pharmacy Taipei Medical UniversityTaipei 11031China Graduate Institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031China

Restenosis is a common complication following coronary angioplasty.The traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut dysbiosis.The aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured rats.As indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of vSMCs.It was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in vSMCs.Meanwhile,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured rats.In conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

关键词： Ascophyllum nodosum Fucus vesiculosus PTEN/PI3K/AKT Restenosis Macrophage Vascular smooth muscle cells Gut microbiota

Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy:a novel delivery system candidate for tumor vaccines

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Science China(Life Sciences) 2024年第4期67卷 680-697页

作者： Nan Li Yun Zhang Miaomiao Han Tian Liu Jinjia Wu Yingxia Xiong Yikai Fan Fan Ye Bing Jin Yinghua Zhang Guibo Sun Xiaobo Sun Zhengqi Dong State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS)Institute of Medicinal Plant Development(IMPLAD)Beijing 100193China Key Laboratory of Bioactive Substances and Resources Utilization of Chinese herbal Medicine from Ministry of Education Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine(Natural Medicine)and Translational MedicineKey Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription from Chinese Academy of Medical SciencesCAMSIMPLADBeijing 100193China Department of Pharmaceutics School of Pharmaceutical SciencesHeilongjiang University of Chinese MedicineHarbin 150036China Jilin Academy of Chinese Medicine Sciences Changchun 130012China Joint research Center for Chinese Medicinal Herbs IMPLADABRC&ACCLBeijing 100193China

The study of tumor nanovaccines(NVs)has gained interest because they specifically recognize and eliminate tumor cells.However,the poor recognition and internalization by dendritic cells(DCs)and insufficient immunogenicity restricted the vaccine efficacy.Herein,we extracted two molecular-weight Astragalus polysaccharides(APS,12.19 k D;APSHMw,135.67 k D)from Radix Astragali and made them self-assemble with OVA257–264directly forming OVA/APS integrated nanocomplexes through the microfluidic method.The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability.APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy.The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution.The FITC-OVA in APS-NVs could be effectively taken up by DCs,and APS-NVs could stimulate the maturation of DCs,improving the antigen cross-presentation efficiency in vitro.The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4.Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.***.injection.Smaller APS-NVs could easily access the lymph nodes.Furthermore,APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells.In addition,APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group.The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region.Subsequently,the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs.Therefore,this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

关键词： Astragalus polysaccharides nanovaccines OVA immunotherapy self-adjuvant

Composition analysis of Compound Shenhua Tablet,a seven-herb Chinese medicine for IgA nephropathy:evaluation of analyte-capacity of the assays

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Chinese Journal of Natural Medicines 2024年第2期22卷 178-192页

作者： ZHANG Haiyan WANG Qiuyue WANG Jianan ZHANG Sichao JIA Weiwei HE Ning XIA Xiaoyan WANG Ting LAI Liyu LI Jiaying DU Jing OLALEYE Olajide E CHEN Xiangmei YANG Junling LI Chuan Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of drug research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy University of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100049China Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People’s Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China Zhongshan Institute for drug Discovery Zhongshan 528400China Haihe Laboratory of Modern Chinese Medicine Tianjin 301617China

Compound Shenhua Tablet,a medicine comprising seven herbs,is employed in treating IgA nephropathy.This study aimed to meticulously analyze its chemical composition.Based on a list of candidate compounds,identified through extensive literature review pertinent to the tablet’s herbal components,the composition analysis entailed the systematic identification,characterization,and quantification of the constituents.The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated.The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents’daily doses.A total of 283 constituents,classified into 12 distinct categories,were identified and characterized in the Compound Shenhua Tablet.These constituents exhibited content levels of 1−10982μg·g^(−1),with daily doses of 0.01−395μmol·d^(−1).The predominant constituents,with daily doses of≥10μmol·d^(−1),include nine organic acids(citric acid,quinic acid,chlorogenic acid,cryptochlorogenic acid,gallic acid,neochlorogenic acid,isochlorogenic acid C,isochlorogenic acid B,and linoleic acid),five iridoids(specnuezhenide,nuezhenoside G13,nuezhenidic acid,secoxyloganin,and secologanoside),two monoterpene glycosides(paeoniflorin and albiflorin),a sesquiterpenoid(curzerenone),a triterpenoid(oleanolic acid),and a phenylethanoid(salidroside).Additionally,there were 83,126,and 55 constituents detected in the medicine with daily doses of 1–10,0.1–1,and 0.01–0.1μmol·d^(−1),respectively.The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine.This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

关键词： Compound Shenhua Tablet Composition analysis Analyte-capacity

Chemical composition, pharmacological activity and development strategies of Rubus chingii: A review

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Chinese herbal Medicines 2024年第3期16卷 313-326页

作者： Xiangmei Xiong Zheng Liu Xiance Che Xuemin Zhang Xia Li Wenyuan Gao Tianjin University of Traditional Chinese Medicine Tianjin Key Laboratory for Modern drug Delivery & High-Efficiency School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin University Key Laboratory of Advanced Chinese Medicine Resources research Enterprises

Raspberries are used for both food and medicine,but it has not yet attracted widespread attention.In this paper,the chemical constituen of the original plant raspberry.R.chingii is one of the new "Zhe Bawei" medicinal materials selected in 2017. "Zhe Bawei" refers to eight kinds of genuine medicinal materials in Zhejiang Province.The chemical constituents,pharmacological effects,processing,and application of Rubus chingii Hu were reviewed to provide a reference for its further development.Relevant literature in recent years was collected in databases such as China Knowledge Network,Web of Science,Elsevier,PubMed,and X-Mol,using "raspberry", "Rubus chingii", "traditional use", "chemical composition", "pharmacology",etc.as keywords individually or in combination.The summary of pharmacological activities shows that the relationship between the pharmacological activities of raspberry is still not deep enough.More in-depth research should be carried out in this direction to explore the mechanism of action of its active ingredients and provide effective reference for the further development of the raspberry industry.In the future,with the participation of more researchers,it is expected to develop innovative drugs based on raspberry for the treatment of diseases.

关键词： applications chemical compositions processing pharmacological effects Rubus chingii Hu

Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2210-2227页

作者： Qing Zhao Junjie Feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong Yanfang Zou Jiali Ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao Guangzhou Key Laboratory of Chinese Medicine research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangdong Engineering research Center of Chinese herbal-derived Vesicles Guangzhou University of Chinese MedicineGuangzhou 510006China Department of Laboratory Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Engineering and Technology research Center for Rapid Diagnostic Biosensors Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai 519000China Department of Blood Transfusion Guangdong Heyou International HospitalFoshan 528306China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关键词： Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling Naringin Bone morphogenetic protein 2 Runt-related transcription factor 2

Protective role of fruits of Rosa odorata var. gigantea against WIRSinduced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis

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Chinese herbal Medicines 2024年第2期16卷 263-273页

作者： Xinnan Liu Zhen Yuan Lifei Luo Teng Wang Feng Zhao Jingze Zhang Dailin Liu National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjin 301617China Tianjin Modern Innovation Chinese Medicine Technology Co. Ltd.Tianjin 300380China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress(WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved.Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin(H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot.Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase(GSH-PX), superoxide dismutase(SOD) and catalase(CAT) contents;anti-inflammatory cytokines interleukin-10(IL-10) and prostaglandin E2(PGE2) levels as well as regulatory factors tumor necrosis factor-a(TGF-a) and somatostatin(SS) contents, while decreasing malondialdehyde(MDA), nitric oxide synthase(i NOS), tumor necrosis factor(TNF-a), interleukin-1β(IL-1β), interleukin-6(IL-6), gastrin(GAS)and endothelin(ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen(PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-ΚB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival.Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of

关键词： anti-apoptosis anti-inflammation anti-oxidation gastric mucosal injury Rosa odorata Sweet var.gigantea(Coll.et Hemsl.)Rehd.et Wils water immersion restrained stress

Bioactive components, pharmacological properties and underlying mechanism of Ganoderma lucidum spore oil: A review

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Chinese herbal Medicines 2024年第3期16卷 375-391页

作者： Jianying Liu Binzhi Zhang Leqi Wang Shasha Li Qinqiang Long Xue Xiao Guangdong Metabolic Diseases research Center of Integrated Chinese and Western Medicine (Institute of Chinese Medicine) Guangdong Pharmaceutical University The Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou Higher Education Mega Center NMPA Key Laboratory for Rapid Testing Technology of drugs Guangdong Institute for Drug Control

Ganoderma lucidum is a Chinese medicinal fungus with a long history of use in healthcare and disease treatment.G.lucidum spores（GLS） are tiny germ cells released from the mushroom cap during the mature stage of growth.They contain all the genetic active substances of G.lucidum.G.lucidum spore oil（GLSO） is a lipid component extracted from broken-walled Ganoderma spores using supercritical CO2extraction technology.GLSO contains fatty acids,Ganoderma triterpenes,sterols and other bioactive compounds.Previous studies have demonstrated that GLSO has a wide range of pharmacological properties,including anti-tumor,anti-aging,neuroprotection,immunomodulation,hepatoprotection and modulation of metabolic diseases.This review summarizes the research progress of GLSO over the past two decades in terms of its bioactive components,extraction and processing techniques,pharmacological effects and safety evaluation.This provides a solid foundation for further research and application of GLSO.

关键词： anti-aging anti-tumor bioactive components Ganoderma lucidum spore oil hepatoprotection immune regulation pharmacological properties

Chemical components in cultivated Cordyceps sinensis and their effects on fibrosis

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Chinese herbal Medicines 2024年第1期16卷 162-167页

作者： Zhonghua Dong Xiao Sun Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalShandong Engineering and Technology Research Center for Pediatric Drug DevelopmentShandong Medicine and Health Key Laboratory of Clinical PharmacyJinan 250014China Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China Shandong Provincial Clinical research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key Laboratory of Emergency and Critical Care Medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineShandong Key Laboratory:Magnetic Field-free Medicine&Functional ImagingQilu Hospital of Shandong UniversityJinan 250012China NMPA Key Laboratory for Clinical research and Evaluation of Innovative drug Qilu Hospital of Shandong UniversityJinan 250012China

Objective:Cultivated Cordyceps sinensis powder has been used as clinical drug and healthy food to nourish the lung and kidney,which solves the problem of serious shortage of wild C.sinensis.This study aims to explore the chemical components and compared their anti-fibrotic effects in cultivated C.sinensis.Methods:Nucleosides,sterols and polysaccharides were separated and purified from cultivated C.sinensis,and analyzed by high performance liquid chromatography,gas chromatography-mass spectrometry and chemical chromogenic methods,respectively.In high glucose-induced rat mesangial cell models,fibronectin and type 1 collagen were used as evaluation indicators.Results:There were 10 kinds of nucleosides and one sterol in cultivated C.sinensis.The contents of nucleosides,sterols and polysaccharides in the cultivated C.sinensis were close to 2%,0.55%and 4.4%,respectively.Furthermore,nucleoside,sterol and polysaccharide components exhibited varying degrees of antifibrotic activity.The nucleoside components and sterol components inhibited the expression of extracellular matrix more effectively in the three main components.Conclusion:Cultivated C.sinensis remains the similar compounds with the wild C.sinensis,and nucleosides and sterols may be the main active substances that contribute to its anti-fibrotic effects.The project of this study may provide valuable information on further optimization of more effective remedies with few side effects based on cultivated C.sinensis.

关键词： anti-fibrotic effects cultivated Cordyceps sinensis ergosterol nucleosides polysaccharides

Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat:In vitro and in vivo studies

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Chinese herbal Medicines 2024年第1期16卷 113-120页

作者： Olabinri P.Folashade Ibrahim Damilare Boyenle Tolulope A.Oyedeji Fiyinfoluwa Demilade Ojeniyi Adisa Ayobami Damilare Leonard O.Ehigie Adeola Folasade Ehigie Membrane Biochemistry and Biophysics research Laboratory Department of BiochemistryLadoke Akintola University of TechnologyOgbomoso 210214Nigeria Computational Biology/drug Discovery Laboratory Department of BiochemistryLadoke Akintola University of TechnologyOgbomoso 210214Nigeria College of Health Sciences Crescent University AbeokutaAbeokuta 111105Nigeria Department of Biochemistry University of LagosLagos 101017Nigeria

Objective:To assess acute toxicity,the in vitro and in vivo effects of methanol and ethyl acetate extracts(JME and JEE)of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.Methods:Acute toxicity of JME and JEE was determined using Lorke’s method.In vitro and in vivo opening of the mitochondrial membrane permeability transition pore(MMPT pore)was spectrophotometrically assayed.Production of malondialdehyde(MDA)as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase(ALP),aspartate and alanine aminotransferase(AST and ALT)and gamma-glutamyl transferase(GGT)was also investigated.Results:JME had an LD_(50) of 3808 mg/kg b.w whereas JEE had an LD_(50) greater than 5000 mg/kg b.***.of rats.After the rats have been fed with both extracts,a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity.From the in vitro and in vivo studies,both extracts prompted intact mitochondria to open their MMPT pores.When compared to the control,lipid peroxide product release and ATPase activity were significantly increased(Pherbal mixture had low toxicity,profound MMPTpore induction,and enhanced ATPase activity,but an increased MDA production.Conclusion:Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis,however,further studies are needed to better clarify the molecular mechanism involved in these phenomena.

关键词： acute toxicity Ageratum conyzoides Linn. apoptosis Hunteria umbellate(K.Schum.)Hallier f. Lepidium meyenii Walp. mitochondrial ATPase mitochondrial lipid peroxidation mitochondrial membrane permeability transition pore polyherbal mixture Xylopia aethiopica(Dunal)A.Rich