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Isoimperatorin alleviates acetic acid-induced colitis in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 147-153页

作者： Saied Goodarzi Amir Hossein Abdolghaffari Behnaz Najafi Mostafa Pirali Hamedani Saeed Tavakoli Mahshad Marvi Maryam Baeeri Narguess Yassa Abbas Hadjiakhoondi Mohammad Abdollahi Zahra Tofighi medicinal plants Research Center Faculty of PharmacyTehran University of Medical SciencesTehranIran department of Toxicology and Pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehranIran department of Pharmacognosy Faculty of PharmacyTehran University of Medical SciencesTehranIran medicinal plants Research Center Institute of Medicinal PlantsACECRKarajIran International Campus School of Pharmacy Tehran University of Medical SciencesTehranIran Toxicology and Diseases group The Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran department of Toxicology and Pharmacology Faculty of PharmacyTehran University of Medical SciencesTehranIran

Objective:To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis rats.Methods:Colitis was induced by intracolonic administration of acetic acid solution(4%v/v)in rats.Rats were divided into six groups including the sham group,the negative control group,the dexamethasone-treated group,and the groups treated with isoimperatorin(0.1,1,and 10 mg/kg/d by gavage).The treatments were administered for three days and then colonic status was assessed by macroscopic,histopathological,and biochemical analyses.Results:Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced colitis.It also significantly reduced myeloperoxidase,TNF-α,IL-1β,and malodialdehyde levels.Conclusions:Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

关键词： Isoimperatorin Inflammatory bowel disease Acetic acid Colitis TNF-α IL-1β

Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity

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Signal Transduction and Targeted Therapy 2024年第2期9卷 693-708页

作者： Tao Yuan Chenming Zeng Jiawei Liu Chenxi Zhao Fujing Ge Yuekang Li Meijia Qian Jiamin Du Weihua Wang Yonghao Li Yue Liu Xiaoyang Dai Jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang Institute of Pharmacology&Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 311199China Ministry of Education Key Laboratory of Chinese medicinal plants Resource from Lingnan Research Center of Medicinal Plants Resource Science and EngineeringGuangzhou University of Chinese MedicineGuangzhou 510006China Center for Drug Safety Evaluation and Research of Zhejiang University Hangzhou 310058China department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310006China department of Oncology Hangzhou Cancer HospitalHangzhou 310002China Cancer Center of Zhejiang University HangzhouChina Engineering Research Center of Innovative Anticancer Drugs Ministry of EducationHangzhouChina

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

关键词： LKB1 inhibiting removing

Molecular regulation of the key specialized metabolism pathways in medicinal plants

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Journal of Integrative Plant Biology 2024年第3期66卷 510-531页

作者： Min Shi Siwei Zhang Zizhen Zheng Itay Maoz Lei Zhang Guoyin Kai Zhejiang Provincial International S&T Cooperation Base for Active Ingredients of medicinal and Edible plants and Health Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and TransformationSchool of Pharmaceutical SciencesJinhua AcademyZhejiang Chinese Medical UniversityHangzhou 310053China department of Postharvest Science Agricultural Research OrganizationVolcani CenterRishonLeZion 7505101Israel department of Pharmaceutical Botany School of PharmacyNaval Medical UniversityShanghai 200433China

The basis of modern pharmacology is the human ability to exploit the production of specialized metabolites from medical plants,for example,terpenoids,alkaloids,and phenolic acids.However,in most cases,the availability of these valuable compounds is limited by cellular or organelle barriers or spatio-temporal accumulation patterns within different plant tissues.Transcription factors(TFs)regulate biosynthesis of these specialized metabolites by tightly controlling the expression of biosynthetic genes.Cutting-edge technologies and/or combining multiple strategies and approaches have been applied to elucidate the role of TFs.In this review,we focus on recent progress in the transcription regulation mechanism of representative high-value products and describe the transcriptional regulatory network,and future perspectives are discussed,which will help develop high-yield plant resources.

关键词： biosynthesis medicinal plants omics secondary metabolism transcription factors

Modulation of the in vitro Oxidative Stress and Erythrocyte Cell Membrane Integrity Using Aqueous, Hydroethanolic and Ethanolic Stem-Barks Extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc

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Pharmacology & Pharmacy 2024年第3期15卷 39-61页

作者： Patrick Hervé Diboue Betote Moustapha Gambo Abdoulaye Francis Ngolsou Esther Del Florence Ndedi Moni Adeline Sabine Fanta Yadang Fidel Castro Lah Weyepe Gabriel A. Agbor Nga Nnanga Maximilienne Ascension Nyegue Laboratory of Pharmacology and Drugs Discovery Centre for Research on Medicinal Plants and Traditional Medicine Institute of Medical Research and Medicinal Plants Studies Yaoundé Cameroon Laboratory of Microbiology Department of Microbiology Faculty of Science University of Yaoundé I Yaoundé Cameroon Multidisciplinary Laboratory Department of Galenical Pharmacy and Pharmaceutical Law Faculty of Medicine and Biomedical Sciences University of Yaoundé I Yaoundé Cameroon department of Physicochemical and Pharmaceutical Sciences Faculty of Health Sciences Abdou Moumouni University Niamey Niger department of Pharmaceutical and Biological Sciences Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Laboratory of Pharmaceutical Technology Centre for Research on Medicinal Plants and Traditional Medicine Institute of Medical Research and Medicinal Plants Studies Yaoundé Cameroon

Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxidants defence system. The aim of this experimental study focused on the capacity of nontoxic aqueous, hydroethanolic and ethanolic extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc. subsp. suaveolens to regulate free reactive species and protein inflammation generated by infectious disease. The phytochemical screenings of G. suaveolens extracts were carried out according to precipitation and colorimetric methods. The total antioxidant and flavonoid contents were determined by the Folin-Ciocalteu and Aluminium Chloride ethanolic methods. The efficiency of G. suaveolens extracts on free radicals was evaluated using DPPH•, ABTS+•, and FRAP methods. The anti-inflammatory properties of extracts were evaluated according to in vitro protein (BSA) denaturation, Proteinase Inhibitory Action, and Red Blood Cell Membrane stabilization assays. The G. suaveolens aqueous, hydroethanolic and ethanolic extracts were used for the acute toxicity assessment according to the OECD protocol. The obtained results showed the presence of flavonoids, phenols, polyphenols, tannins, anthocyanins, alkaloids, terpenoids, and sterols as secondary metabolites families in G. suaveolens extracts. The highest contents of total antioxidants and flavonoids were highlighted in the hydroethanolic extract. However, it’s the G. suaveolens aqueous extract that showed the best free radical DPPH• and ABTS+• scavenging activities (SC50) of 11.06 μg/mL and 15.16 μg/mL respectively. The highest ferric-reducing activity was found in G. suaveolens ethanolic extract with 866.23 μg EGA/mg of dry weight. The hydroethanolic extract has shown a high anti-inflammatory activity through BSA denaturation and erythrocyte membrane haemolysis with inhibitory concentrations 50 (IC50) of

关键词： Greenwayodendron suaveolens Secondary Metabolites Oxidative Stress Antioxidant Activity Anti-Inflammatory Properties and Oral Acute Toxicity

Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

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Chinese Journal of Natural Medicines 2024年第3期22卷 265-272页

作者： XU Shuangyu ZHANG Feng TAO Linlan JIANG Yangming HUANG Tao LI Yanan HU Zhanxing YANG Jue HAO Xiaojiang YUAN Chunmao State Key Laboratory of Functions and Applications of medicinal plants Guizhou Medical UniversityGuiyang 550014China School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang 550025China Natural Products Research Center of Guizhou Province Guiyang 550014China State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China

Four new sesquiterpene lactones(SLs)(1–4),along with a biosynthetically related SL(5),have been isolated from the leaves of Magnolia grandiflora.Magrandate A(1)is notable as the first C18 homogemarane type SL,featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core.Compounds 2 and 3,representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products,were also identified.The structures of these isolates were elucidated through a combination of spectroscopic data analysis,electronic circular dichroism calculations,and X-ray single-crystal diffraction analysis.All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells.Notably,3–5 showed a significant inhibitory effect on nitric oxide production,with IC50 values ranging from 0.79 to 4.73μmol·L^(−1).Additionally,4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines,with IC50 values between 3.09 and 11.23μmol·L^(−1).

关键词： Magnolia grandiflora Sesquiterpene lactones Isolation and identification Anti-inflammatory activity

A review:the mechanism of plant-derived polysaccharides on osteoblasts and osteoclasts

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未来食品学报(英文) 2024年第3期4卷 183-192页

作者： Mengjie Ren Adel F.Ahmed Meng Li Menghan Li Zhiruo Yan Jinmei Wang National R&D Center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Joint International Research Laboratory of Food&Medicine Resource Function Henan ProvinceKaifeng 475004China medicinal and Aromatic plants Researches department Horticulture Research InstituteAgricultural Research CenterGiza 12511Egypt

Bone loss and deterioration of bone microarchitecture would increase the bone fragility and fracture risk,leading to the osteoporosis.More and more evidences proved that plant-derived polysaccharides could have a remarkable influence on osteoblasts and osteoclasts,exerting anti-osteoporosis effects.According to the previous research,the extract of Cibotium barumoz,Achyranthes bidentata,Curculigo orchioides,Epimedium brevicornum,Angelica sinensis,Polygonatum sibiricum,Dendrobium officinale,Morinda officinalis,Nelumbo mucifera,Diospyros kaki,Hordeum vulgare,Cistanche deserticola,Commiphora Myrrha and other plant-derived polysaccharides could benefit to the osteoblasts and osteoclasts.The essential mechanisms are mainly related to the activation or inhibition of many factors,including runt-related transcription factor 2(Runx2),B-catenin,osterix(Osx),activator protein-1(AP-1),osteocalcin(OCN/BGP),alkaline phosphatase(ALP),osteopontin(OPN),bone morphogenetic protein(BMP),phosphatidylinositol 3-kinase(PI3K)/C-Jun N-terminal kinase(JNK)/extracellular regulated protein kinase(ERK),osteoprotegerin(OPG),receptor activator of nuclear factor-kB(RANK),monocyte/macrophage colony-stimulating factor(M-CSF),tumor necrosis factor receptor-associated factor 6(TRAF-6),receptor activator of nuclear factor(NF)-KB ligand(RANKL),nuclear factor of activated T cells 1(NFATc1),c-Fos,matrix metallopeptidase-9(MMP-9),glycogen synthase kinase 3β(GSK3B)/B-catenin,nuclear factor E2-related factor 2(Nf2),as well as these related pathways,such as Wnt/p-catenin,BMP-2/SMAD1/5/8,PI3K/AKT,OPG/RANKL/RANK,NF-κB,MAPKs,etc.These plant-derived polysaccharides could improve the dynamic balance of bone formation and resorption through promoting the differentiation and maturation of osteoblast or inhibiting its formation.The reviewed plant-derived polysaccharides and their regulating mechanisms on the osteoclasts and osteoblasts provide the evidences for the development of osteoporosis therapeutics.

关键词： Osteoporosis Plant-derived polysaccharides Osteogenesis promotion Osteoclasts inhibition

Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of medicinal plants The Chinese University of Hong KongHong KongChina department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary glands.Sixty-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological activities.Moreover,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response(P<

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

Using Network Pharmacology to Explore Therapeutic Effect of Polygonum capitatum on Renal Calculus in Rats

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medicinal Plant 2024年第3期15卷 45-49页

作者： Bo TU Xu ZHANG Yan LIN Huang YANG Minghui HE Engineering Research Center of Chronic Disease Prevention and Treatment of Authentic medicinal Materials in Guizhou Higher Education Institutions School of Pharmaceutical SciencesGuizhou Medical UniversityGuiyang 550025China State Key Laboratory of Functions and Applications of medicinal plants Guizhou Medical UniversityGuiyang 550004China

[Objectives]To explore the therapeutic effect of Polygonum capitatum on renal calculus in rats based on network pharmacology.[Methods]Through the preliminary construction of P.capitatum-urolithiasis disease target network,explore the active components,action pathway and action target of P.capitatum-urolithiasis treatment,and use 1%ethylene glycol+2%ammonium chloride to induce SD rat kidney calcium oxalate stone model to verify the efficacy of P.capitatum-urolithiasis treatment.[Results]Through the network pharmacological prediction,it is found that the important active components in P.capitatum were quercetin,gallic acid,rutin,silybin,catechin,kaempferol and so on;potential active targets include INS,CAT,IL-6,MOCOS,etc.The results also suggest that forkhead transcription factor signaling pathway(FoxO signaling pathway),tumor necrosis factor signaling pathway(TNF signaling pathway)and hypoxia-inducible factor signaling pathway(HIF-1 signaling pathway)are the core pathways.The results of biochemical indicators in animal experiment showed that the contents of serum urea nitrogen(BUN),creatinine(Cr)and malondialdehyde(MDA)in renal tissue in the treatment group(200,500 mg/kg)were significantly lower than those in the model group,while the content of superoxide dismutase(SOD)was significantly higher than that in the model group.In addition,the kidney tissue H&E staining sections showed that P.capitatum alcohol extract administration group rats kidney calcium oxalate crystals were significantly reduced compared with the model group,the degree of renal tubular lumen expansion was lighter than the model group,suggesting that P.capitatum alcohol extract has the effect of improving renal calculus in rats.[Conclusions]This study provides a theoretical reference for the deep development of P.capitatum in the treatment of renal calculus.

关键词： Polygonum capitatum Urolithiasis Network pharmacology

Poisonous plants of the Karakalpak Part of the Ustyurt Plateau (Uzbekistan)

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American Journal of Plant Sciences 2024年第2期15卷 83-94页

作者： Aymuratov Rapat Abduraimov Ozodbek Shomurodov Habibullo Abduraimov Azizbek Adilov Bekzod Karakalpak Scientific Research Institute of Natural Sciences of The Karakalpak Branch of The Academy of Sciences of The Republic of Uzbekistan Nukus Uzbekistan Institute of Botany Academy Science Republic of Uzbekistan Tashkent Uzbekistan department of medicinal plants and Botany Faculty of Natural Science Gulistan State University Gulistan Uzbekistan

The article presents the composition and current state of poisonous plants distributed on the Ustyurt plateau. Ustyurt is one of the largest deserts in Central Asia, differing from other deserts of the world in geographical location, relief, flora and fauna and other features. The territory of Ustyurt occupies 21.3 million hectares, of which the Karakalpak part accounts for 7.2 million hectares. Poisonous alkaloid-bearing plants of the Karakalpak part of the Ustyurt plateau Anabasis aphylla, Atriplex flabellum, Kalidium capsicum, Salsola arbusculaeformis, Salsola foliosa, Aellenia subaphylla, Anabasis brachiata, Rheum tataricum, Capparis spinosa, Glycyrrhiza aspera. Alkaloid-bearing plants that are not eaten or poorly eaten by cattle Ephedra distachya, Delphinium songaricum, Anabasis salsa, alkaloid-bearing plants eaten by animals without harm Carex physodes, Eremopyrum orientale, Agrophyllum repens, Astragalus amodendron, Astragalus villosissimus, species of the genera Calligonum, Salsola. Poisonous plants of the Karakalpak part of the Ustyurt plateau. An analysis of the pasture flora of the Karakalpak part of the Ustyurt plateau shows that 62 species of wild poisonous plants belonging to 49 genera and 19 families grow here. Although these plants are considered poisonous, but in modern pharmaceutics and medicine, they are used as medicinal.

关键词： Ustyurt Plateau Species Poisonous Desert Climate Change