JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Xianbang Hou,Ran Chen,Juan Wu,Yujie Huang,Xueyuan Zhang,Shaobao Xu,Liwei He
Ethnopharmacological relevance Isatis tinctoria L. (Isatidis Radix) is a type of Chinese medicine used to treat various inflammations. Lignans are the main active ingredients of Isatidis Radix, which exhibit potent anti-inflammatory properties. However, the targets underlying the anti-inflammatory effects of Isatidis Radix remain unclear. Aim of the study The objective of this research was to investigate the active constituents of Isatidis Radix and the molecular mechanisms behind its anti-inflammatory properties. Materials and methods Firstly, Liquid Chromatography-Mass Spectrometry (LC-MS), network pharmacology, and molecular docking were employed to identify the active ingredients and key targets of Isatidis Radix lignans and predict their underlying anti-inflammatory mechanisms. Secondly, the enzyme-linked immunosorbent assay (ELISA) and the LPS-induced cell model were employed to verify the selective inhibitory effect of the active ingredients on the key target COX-2. Finally, the analgesic and anti-inflammatory effects were evaluated using the hot-plate test, acetic acid-induced writhing, complete Freund’s adjuvant-induced paw edema, and xylene-induced ear edema assays. Results A total of 24 compounds were found to be absorbed into the bloodstream, including 15 prototype components and 9 metabolites, as determined by LC-MS analysis. Furthermore, Network pharmacology analysis revealed that COX-2 served as the central target in the anti-inflammatory mechanism of Isatidis Radix lignans. Lariciresinol, a class of lignans derived from Isatidis Radix, selectively inhibited COX-2 and reduced inflammatory marker production in vitro and in vivo . It significantly increased the incubation period of heat pain, reduced writhing frequency, and decreased the severity of ear and foot swelling. Moreover, lariciresinol had no obvious gastrointestinal side effects and was not toxic to cardiomyocytes. Conclusion Our study indicates that Isatidis Radix lignans exert their anti-inflammatory effect by selectively inhibiting the COX-2 enzyme and confirms lariciresinol as a natural selective COX-2 inhibitor.
研究领域:
中药学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2025
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IF 5.9
Zi-Jie Song,Xiao-Fei Wu,Zhi-Ya Zhou,Jing-Jing Zhang,Yan-Yan Pan,Xue Dong,Xuan Pang,Ya-Ping Xie,Juan Sun,Yu Zhang,Jie Qin
A library comprising twenty-four isosteric derivatives of celecoxib substituted with carboxylic acid (labeled as 5a - 5x ), was synthesized and characterized through 1 H NMR, 13 C NMR, HRMS, and elemental analysis. Molecular docking studies revealed that all compounds successfully docked into the binding pocket of COX-2, and the introduction of carboxyl group enhances the interaction between the derivatives and COX-2. The compounds were further evaluated for cell toxicity, and in vitro anti-inflammatory activity. Notably, compound 5l exhibited significant inhibition of both COX-2 and NO release in vitro in comparison to the standard compound, displaying the highest selectivity towards the COX-2 enzyme (SI = 295.9) in comparison to celecoxib (SI = 261.3). 5l also exhibited the most potent anti-inflammatory activity and safety (ulcer index = 5.2) in vivo comparable to celecoxib at the same concentration. Through the molecular modeling and dynamics analysis, it was observed that compound 5l effectively stabilized within the active binding site of COX-2 through strong hydrogen bond interactions, and through the ADMET studies investigated the physiochemical properties and drug-likeliness behavior of compound 5l . In conclusion, compound 5l demonstrated to be a potential selective COX-2 anti-inflammatory candidate with reduced gastrointestinal risks.
研究领域:
药理学
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药物化学
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炎症研究
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DOI
PubMed
高影响因子
FITOTERAPIA
·
2019
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IF 2.431
Jingwen Li,Menglong Duan,Xinsheng Yao,Danmei Tian,Jinshan Tang
Phytochemical studies of the air-dried pericarp of Citrus grandis led to the isolation of four new compounds including three prenylated benzenepropanoic acids ( 2 , 3 and 5 ) and one alkamidic glycoside ( 6 ), together with ten known compounds ( 1 , 4 and 7 – 14 ). The structures of these compounds were determined by the NMR spectroscopy, optical rotation data and modified Mosher's method. Meanwhile, the anti-neuroinflammatory activities of all isolated compounds were evaluated by detecting the production of nitric oxide (NO) in LPS-stimulated BV2 cells. The results showed that compounds 1 , 2 , 5 and 13 exhibited strong inhibition effects on NO production in LPS-stimulated BV2 cells. Mechanistically, compounds 1 , 2 and 5 could suppress the expressions of iNOS. In addition, compounds 1 , 2 and 5 also showed obvious inhibition effects on COX-2 expression, another vital enzyme in the inflammation process, in LPS-treated BV2 cells. These findings shed light on the potent anti-neuroinflammatory effects of Citrus grandis .
研究领域:
药理学
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神经科学
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植物化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
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IF 5.811
Zhang Yu,Su Na,Liu Weiyi,Wang Qingqing,Sun Jianguo,Peng Ying
Dysmenorrhea refers to a kind of uterine cramping pain that occurs in women during the period of menstrual. Guizhi Fuling Capsules are mainly used for the treatment of various pain syndromes and especially effective in treating primary dysmenorrhea. However, the research on its modern pharmacology and mechanism of action have not been thoroughly carried out. It is not clear about the main active ingredients, potential targets and metabolic pathways involved in its efficacy. Therefore, this research project employed estradiol benzoate sensitization combined with oxytocin pain to construct the cold coagulation syndrome dysmenorrhea model, observed the anti-dysmenorrhea effect of Guizhi Fuling Capsules, and used the metabolomics to explore its mechanism. The results showed that Guizhi Fuling Capsules could considerably reduce the number of writhing times in dysmenorrhea rats, increasing the level of PGE2 and β-EP and reducing the contents of PGF2α in rat serum. Pathological sections of uterus and ovaries also showed that Guizhi Fuling Capsules could significantly relieve endometrial hyperplasia and improve ovarian function. The LC/MS-based metabolomics of rat uterine indicated that the model group has a great deviation from the control group. Compared with the model group, the Guizhi Fuling Capsules group had a tendency to shift to the control group, and the main metabolic changes was mainly concentrated on saturated and unsaturated fatty acids. Among them, arachidonic acid is in a pivotal position, and the expression of its rate-limiting enzyme (COX-2) involved in its cyclooxygenase metabolic pathway was significantly up-regulated in the model group, but significantly decreased after the intervention of Guizhi Fuling Capsules. In conclusion, Guizhi Fuling Capsules can effectively relieve primary dysmenorrhea, and this effect may be attributed to the regulation effects of Guizhi Fuling Capsules on endogenous metabolism, such as inhibiting arachidonic acid converted to prostaglandins through downregulate the expression of COX-2, which plays an anti-inflammatory effect.
研究领域:
药理学
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中医药学
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代谢组学
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妇科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Amina Arken,Xinmin Zhao,Yanhua Gao,Adil Omar,Dan Tang,Ahmidin Waili,Zi Yang,Yahui Wang,Haji Akbar Aisa,Abulimiti Yili
Ethnopharmacological relevance Lamb abomasum is used as an edible medicinal source in traditional Chinese medicine for the treatment of gastrointestinal disorders . Lamb abomasum sourced biochemical drug Lamb's trip extract and Vitamin B12 capsule used for the clinical treatment of chronic gastritis , gastric ulcer , and reversal of intestinal metaplasia . Therefore, claimed to have prevention of gastric cancer activity. Aim of the study In this study, we aim to assess whether the glycoprotein has biological activity in the cure of gastric disorder and conduct a structure-activity relationship. Materials and methods Glycoproteins’ extraction conditions were optimized by the response surface method and purified with DEAE-cellulose and Sephadex G-50 chromatography. Two homogenous glycoproteins’ physiochemical structures were studied with electrophoresis , HPLC analysis, peroxide oxidation, and β-elimination, FT-IR, CD, LC-MS/MS, and EDS analysis. The antiinflammation activity of the glycoprotein was determined against COX-2 and LOX-15 enzyme inhibitory ability in vitro, and antitumor activity against HT-29 and HGC-25, and cytotoxicity on L-02 cells was determined in vivo with the MTT method. Results The abomasum was abundant in glycoprotein and the extraction yield of glycoprotein was up to 24.6 ± 2.1% under optimized conditions. Two homogeneous glycoproteins SAGP-I and SAGP-II determined to be ribose-conjugated and sulfated glycoproteins with a molecular weight of 15.6 kDa and 6.4 kDa. And according to the structural analysis, SAGP-I was a mucin-type ribose-conjugated glycoprotein with 14 O-glycosylation and one N- glycosylation site. SAGP-I and SAGP-II have remarkable anti-inflammatory activity against COX-2 enzyme with the IC 50 of 17.64 ± 1.25 μ g/mL and 16.14 ± 1.11 μ g/mL, respectively. Meanwhile, the two glycoproteins showed strong antitumor activity against HT-29 with the EC 50 of 19.19 ± 1.46 μ g/mL and 184.9 ± 5.6 μ g/mL, respectively. Conclusion The Highly purified glycoprotein SAGP-1 and SAGP-II showed anti-inflammatory activity against the COX-2 enzyme, and antitumor activity against HT-29 human colon cancer cells and noun-inhibitory activity against LOX-15 enzyme and HGC-25. Both glycoproteins are ribose conjugated and sulfated whose characters are related to their anti-inflammatory and anti-tumor activity. Such results suggest the possibility of anti-inflammatory and pre-cancer activity. And in some degree explains the pharmacy of abomasum's traditional use in gastric disorder and clinical use of lamb abomasum APIs drugs’ in gastric disorders and gastric cancer development. This study provides a preliminary basis for the further study of the per-cancer mechanism of lamb abomasum glycoprotein. And, would be the material basis of the clinical use of Lamb's trip extract and Vitamin B12 capsule.
研究领域:
药理学
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生物化学
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民族药理学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
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2022
·Vol. 51
·期 33
·12604-12619
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IF 4.569
Zuojie Li,Linming Li,Wenhuan Zhao,Bin Sun,Zhifang Liu,Min Liu,Jun Han,Zhengping Wang,Dacheng Li,Qingpeng Wang
To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(IV) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2. It exerts remarkable DNA damage after reduction to platinum(II) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3+ and CD8+ T cells in tumor tissues.
研究领域:
药理学
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肿瘤学
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化疗
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药物开发
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癌症生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Zhang Yiling,Li Yu,Lu Jiayu,Qin Xin,Wang Zixin,Cai Aojie,Fan Ling,Jin Ronghua,Xie Yandong
To address the therapeutic limitations and metabolic toxicity associated with conventional nanocarriers, a nanostructure using an “MOF-in-MOF” strategy was engineered. The comprises an olsalazine (Olsa)-based copper metal-organic framework (Olsa-MOF) that integrates intrinsic anti-inflammatory properties and enhanced chemodynamic performance. This Olsa-MOF template is integrally enveloped by a tumor microenvironment-responsive TK-based Cu-MOF layer, which demonstrates exceptional photothermal properties. Subsequent surface functionalization with dopamine-grafted hyaluronic acid (DOPA-HA) endows active targeting ability, yielding the final nanocomposite termed Olsa@TK-Cu@HA. Olsa@TK-Cu@HA not only overcomes the limitations of conventional nanocarriers but also offers a novel strategy to enhance the therapeutic efficacy of photothermal therapy (PTT) and chemodynamic therapy (CDT) through targeted modulation of the COX-2/PGE2 inflammatory axis. The Olsa@TK-Cu@HA demonstrates a superior photothermal conversion efficiency (26.8%) and robust reactive oxygen species (ROS) generation, along with pH-responsive release of Olsa. In vitro evaluation demonstrated that Olsa@TK-Cu@HA exerts tumor-selective cytotoxicity, showing 3.5-fold higher potency against cancer cell. Moreover, Olsa@TK-Cu@HA effectively induces immunogenic cell death (ICD), as evidenced by increased extracellular ATP efflux (5.06-fold elevation) and CRT exposure. Concurrently, it downregulates the COX‑2/PGE2 axis to relieve immunosuppression in the tumor microenvironment and suppresses PD‑L1 expression. This coordinated action amplifies ICD‑mediated antitumor immunity, leading to a tumor regression rate of 84.0% in vivo. By integrating precision targeting, stimulus-responsive drug release, and immunometabolic reprogramming, this work moves beyond conventional treatment paradigms and establishes an innovative platform for next‑generation cancer therapy. Graphical The alternative text for this image may have been generated using AI.
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2022
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IF 4.631
Huixia Feng,Guilin Chen,Yongli Zhang,Mingquan Guo
Background Dysosma versipellis ( D. versipellis ) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown. Purpose This study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action. Methods Bioaffinity ultrafiltration coupled to liquid chromatography–mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis , and then further validation was conducted using in vitro inhibition assays and molecular docking. Results A total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC 50 value at 0.36 ± 0.02 μM lower than indomethacin at 0.73 ± 0.07 μM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC 50 value at 104.79 ± 8.26 μM comparable to quercetin 3- O -glucoside at 135.25 ± 6.54 μM. Conclusion We firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants.
研究领域:
药理学
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生物化学
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传统医学
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植物科学
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产品关联
DOI
PubMed
高影响因子
Journal of Essential Oil Bearing Plants
·
2020
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IF 0.824
Yu Chen,Lejing Chi,Xiaoxin Liang,Yaohui Shi,Tongyun Wu,Mao Ye,Ping Han,Li Lin,Lanyue Zhang,Peng Xu,Zhiyun Du
Cedrus deodara is a cedar plant from the Pinaceae family. Because Cedrus is widely used in health care products, cosmetics, medicine, and insecticides, the essential oils of Cedrus deodara (CDEOs) are gaining increasing levels of attention. However, there have only been a few studies on the anti-inflammatory effects of CDEOs. This study aimed to systematically study the composition and biological effects of CDEOs, in line with this, the study assessed the chemical composition of CDEOs and evaluated their anti-inflammatory mechanisms in mice. Gas chromatography-mass spectrometry (GC-MS) was used to determine and analyze a total of 41 compounds from CDEOs. It was found that the major components of CDEOs are thujopsene (28.23%), α-cedrene (17.01%), and cedrol (15.55%); moreover, our results showed that the active ingredients in CDEOs have anti-inflammatory and antioxidant effects and that the active ingredients in CDEOs can be used as an antioxidant, as an important biological resource in functional food, and as ingredients in cosmetics and pharmaceuticals. Taken together, these CDEOs serve as ideal additives for anti-inflammatory drugs.
研究领域:
药理学
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植物化学
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炎症研究
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DOI
高影响因子
BIOMATERIALS
·
2026
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IF 13.6
Dandan Mi,Tiantian Liu,Lan Zou,Yuyu Wei,Jun Zeng,Chunxiao Nie,Yi Zeng,Rujing Wang,Mengnan Zhao,Sanjun Shi
Surgical resection combined with chemotherapy remains the standard clinical intervention for triple-negative breast cancer (TNBC). However, the elevated expression of COX-2/PGE 2 , often exacerbated by chemotherapeutic agents, is significantly associated with high postoperative recurrence and metastasis. Tailored for the TNBC postoperative setting, we developed a photopolymerizable, dual-asymmetric hemostatic Janus hydrogel patch (DJ-Patch) based on the synergistic pharmacodynamic rationale of gambogic acid (GA) and celecoxib (CXB) pairing. The DJ-Patch exhibits a stratified bilayer configuration comprising a rapid-release layer (5% GelMA) encapsulating GA, juxtaposed with an extended-release layer (10% GelMA/2.5% PEGNB) containing the selective COX-2 inhibitor CXB. In vitro study corroborated this differential release modality, revealing asymmetric kinetics wherein GA achieved ∼20% release at 8 h escalating to greater than 60% by day 3, whereas CXB demonstrated ∼10% release at 8 h and ∼30% by day 3. In vivo release profiles further substantiated these findings, demonstrating that CXB exhibited a 2-fold prolonged release duration relative to GA. The asymmetric adhesive design, featuring a high-adhesion interface manifesting adhesion strength 12.5-fold superior to GelMA alone, facilitated rapid intraoperative hemostasis with clotting time reduced to 160 s versus 440 s in untreated controls, and effected efficacious wound sealing as validated in a mouse liver laceration model. In an orthotopic 4T1-Luc TNBC resection model, the DJ-Patch achieved 86% survival, complete tumor clearance by day 7, and suppressed lung metastasis through sustained COX-2/PGE 2 axis inhibition, Treg cell reduction, and remodeled the immunosuppressive tumor microenvironment (TME). Collectively, this integrated platform offers a promising strategy for comprehensive TNBC postsurgical management.
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2019
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IF 4.833
Zhang Li,Zhong-Chang Wang,Xin Li,Muhammad Abbas,Song-Yu Wu,Shen-Zhen Ren,Qi-Xing Liu,Yi Liu,Peng-Wen Chen,Yong-Tao Duan,Peng-Cheng Lv,Hai-Liang Zhu
In this paper, 41 hybrid compounds containing diaryl-1,5-diazole and morpholine structures acting as dual COX-2/5-LOX inhibitors have been designed, synthesized and biologically evaluated. Most of them showed potent antiproliferative activities and COX-2/5-LOX inhibitory in vitro. Among them, compound A33 displayed the most potency against cancer cell lines (IC 50 = 6.43–10.97 μ M for F10, HeLa, A549 and MCF-7 cells), lower toxicity to non-cancer cells than celecoxib ( A33 : IC 50 = 194.01 μ M vs. celecoxib : IC 50 = 97.87 μ M for 293T cells), and excellent inhibitory activities on COX-2 (IC 50 = 0.17 μ M) and 5-LOX (IC 50 = 0.68 μ M). Meanwhile, the molecular modeling study was performed to position compound A33 into COX-2 and 5-LOX active sites to determine the probable binding models. Mechanistic studies demonstrated that compound A33 could block cell cycle in G2 phase and subsequently induced apoptosis of F10 cells. Furthermore, compound A33 could significantly inhibit tumor growth in F10-xenograft mouse model, and pharmacokinetic study of compound A33 indicated that it showed better stability in vivo . In general, compound A33 could be a promising candidate for cancer therapy.
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2022
·Vol. 46
·期 12
·e14460
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IF 3.654
Jing Guo,Jian-Kai Tang,Bai-Fang Wang,Wen-Rui Yan,Ting Li,Xue-Jian Guo,Lei Zhang,Tao Wang,Qian-Yun Sun,Li-Wei Zhang
Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1β, NO, and PGE 2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. Practical applications Phillygenin is one of the major active ingredients in Forsythia suspensa . But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.
研究领域:
药理学
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炎症
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疼痛管理
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天然产物
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传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）