Last update 01 Nov 2024

ROS1 x IL-1β x TNF-α x IL-6 x COX-2

Last update 01 Nov 2024

Basic Info

Related Targets

ROS1IL-1βTNF-α[+2]

Drugs associated with ROS1 x IL-1β x TNF-α x IL-6 x COX-2

GCAP-001

Target

COX-2 x IL-1β x IL-6 x ROS1 x TNF-α

Mechanism

COX-2 inhibitors [+4]

Active Org.

Goodcap Pharmaceuticals, Inc.Startup

Originator Org.

Goodcap Pharmaceuticals, Inc.Startup

Active Indication

Neuroinflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ROS1 x IL-1β x TNF-α x IL-6 x COX-2

100 Translational Medicine associated with ROS1 x IL-1β x TNF-α x IL-6 x COX-2

0 Patents (Medical) associated with ROS1 x IL-1β x TNF-α x IL-6 x COX-2

Literatures (Medical) associated with ROS1 x IL-1β x TNF-α x IL-6 x COX-2

01 Dec 2024·Bioorganic Chemistry

Biologically active franchetine-type diterpenoid alkaloids: Isolation, synthesis, anti-inflammatory, agalgesic activities, and molecular docking

Article

Author: Xiao, Yan ; Chang, Ye ; Huang, Shuai ; Zhou, Xian-Li ; Liu, Yu-Yan ; Yuan, Cheng ; Qu, Wen-Rong ; Li, Ting-Ting ; Chen, Lin

In this study, four franchetine-type diterpenoid alkaloids (1-4) were isolated from Aconitum sinoaxillare, and fourteen diverse franchetine analogs (5-18) were synthesized. Compounds 1, 2, 7 and 16 exhibited stronger inhibitory effects on NO production when compared to celecoxib. Among them, compound 1 had the best inhibitory effect on iNOS and COX-2 inflammatory proteins. The in vitro studies displayed that the anti-inflammatory effect of the most active compound 1 was ascribed to the inhibition of the TLR4-MyD88/NF-κB/MAPKs signalling pathway. Consequently, this led to a inhibition in the expression of inflammatory factors or mediators including NO, ROS, TNF-α, IL-6, IL-1β, iNOS, and COX-2. Additionally, compound 1 had low toxicity (LD₅₀ > 20 mg/kg) in mice, and it had notable analgesic effects on acetic acid-induced visceral pain (ED₅₀ = 2.15 ± 0.07 mg/kg). Moreover, compound 1 exhibited a distinct reduction in the Na_V1.7 and Na_V1.8 channel currents during both resting and half-inactivated states at 50 μM. The present study enriches the pharmacological activities of franchetine derivatives and provides valuable insights for the development of novel anti-inflammatory and analgesic agents.

01 May 2024·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

[Mechanism of total saponins of Panax japonicus against liver injury induced by acetaminophen in mice based on ERK/NF-κB/COX-2 signaling pathway].

Article

Author: Ren, Jian-Xia ; Zhang, Ji-Hong ; Tan, Fa-Ming ; Liu, Ying ; Zhou, Gang ; Chen, Mao-Hua ; Shi, Meng-Qiong ; Tang, Hai-Ming ; Bao, Zhong-Wen ; Hu, Hui-Quan ; Guo, Wei ; Wang, Jun-Zhi

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1β, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1β, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1β, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.

01 Apr 2024·Journal of Ethnopharmacology

Enzyme-treated red rice (Oryza sativa L.) bran extracts mitigate inflammatory markers in RAW 264.7 macrophage cells and exhibit anti-inflammatory efficacy greater/comparable to ferulic acid, catechin, γ-tocopherol, and γ-oryzanol

Article

Author: Jayadeep, A ; I, Sapna

ETHNOPHARMACOLOGICAL RELEVANCERice (Oryza sativa L.), a staple food for a significant portion of the global population, has been recognized for its traditional medicinal properties for centuries. Rice bran, a by-product of rice milling, contains many bioactive compounds with potential pharmaceutical and therapeutic benefits. In recent years, research has highlighted the anti-inflammatory potential of rice bran, contributed by the bioactive components concentrated in their bran but, unfortunately, entrapped in the bran matrix, with limited bioavailability. Previous studies have reported that the enzymatic treatment of rice bran improves the bran's bioactive compound profile but did not investigate its impact on chronic conditions such as inflammation.AIM OF THE STUDYThis study investigates the anti-inflammatory effects of endo-1,4-β-xylanase (ERB) and Viscozyme (VRB) treated red rice bran extracts against lipopolysaccharide-induced inflammation in RAW264.7 macrophages in comparison with non-enzyme-treated bran (CRB). Further established their efficacy with known anti-inflammatory compounds-ferulic acid (FA), catechin (CAT), γ-tocopherol (GTP), and γ-oryzanol (ORZ).MATERIALS AND METHODSThe RAW 264.7 macrophage cells were pre-treated with non-toxic concentrations (10-200 μg/mL) of FA, CAT, GTP, ORZ, CRB, ERB, and VRB, followed by inflammatory stimulation with LPS for 24 h. Further, the cell supernatant and pellets were harvested to study the anti-inflammatory effects by evaluating and measuring their efficacy in inhibiting pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IL-1β) and mediators (ROS, NO, PGE2, COX2, iNOS) through biochemical, ELISA, and mRNA expression studies.RESULTSThe findings showed that both ERB and VRB effectively inhibited the production of pro-inflammatory markers (TNF-α, IL-6) and mediators (ROS, NO, PGE2) by downregulating mRNA expressions of inflammatory genes (TNF-α, IL-1β, IL-6, IL-10, COX2, iNOS) and demonstrated anti-inflammatory efficacy higher than CRB. On comparison, ERB demonstrated exceptional efficacy by causing a reduction of 48% in ROS, 20% in TNF-α, and 23% in PGE2 at 10 μg/mL, surpassing the anti-inflammatory capabilities of all the bioactive compounds, FA and ORZ, respectively. At the same time, VRB exhibited remarkable efficacy by reducing NO production by 52% at 200 μg/mL and IL-6 by 66% at 10 μg/mL, surpassing FA, CAT, ORZ, and GTP. Further, ERB downregulated the mRNA expression of IL-10 and iNOS, while VRB downregulated TNF-α, IL-1β, and COX2 expression. Both extracts equally downregulated IL-6 expression at 10 μg/mL, demonstrating the efficacy more remarkable/on par with established anti-inflammatory compounds.CONCLUSIONSOverall, enzyme-treated rice bran/extract, particularly ERB, possesses excellent anti-inflammatory properties, making them promising agents for alternatives to contemporary nutraceuticals/functional food against inflammatory diseases.

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