Structurally Modified Glycyrrhetinic Acid Derivatives as Anti-inflammatory Agents

2020 ◽  
pp. 104598
Author(s):  
Ming Bian ◽  
Dong Zhen ◽  
Qing-Kun Shen ◽  
Huan-Huan Du ◽  
Qian-Qian Ma ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Haiming Chen ◽  
Huazhen Liu ◽  
Bin Tang ◽  
Yuchao Chen ◽  
Ling Han ◽  
...  

Psoriasis is recognized as an autoimmune and inflammatory dermatosis, which is estimated to affect 2-3% of the population worldwide. 18β-Glycyrrhetinic acid (GA), one of the main ingredients of Licorice (Glycyrrhiza glabra L.), has been shown to have numerous pharmacological effects such as antioxidative, antitumor, and anti-inflammatory activities. However, it remains to be explored whether GA has antipsoriatic effect on psoriasis. In this study, we evaluated the protective effect of GA on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse model. Results indicated that GA dramatically improved psoriatic lesions and reduced psoriasis area and severity index scores. GA also suppressed the mRNA levels of IL-6, TNF-α, IL-17, IL-23, and IL-1β in the skin and increased the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens. Its anti-inflammatory and immunomodulatory activities may be related to its suppression of the STAT3 and mTOR signaling. In conclusion, GA ameliorated the symptoms of psoriasis, at least in part, through inhibition of inflammatory cytokines and STAT3/mTOR signaling and activation of Tregs in both lymph nodes and spleens. These effects are expected to be beneficial in the treatment and prevention of psoriasis.


2020 ◽  
Vol 101 ◽  
pp. 103985 ◽  
Author(s):  
Yang Yang ◽  
Qiuyan Zhu ◽  
Yingying Zhong ◽  
Xiping Cui ◽  
Zhengyun Jiang ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2406 ◽  
Author(s):  
Andrey V. Markov ◽  
Aleksandra V. Sen’kova ◽  
Oksana V. Salomatina ◽  
Evgeniya B. Logashenko ◽  
Dina V. Korchagina ◽  
...  

Semi-synthetic triterpenoids, bearing cyano enone functionality in ring A, are considered to be novel promising therapeutic agents with complex inhibitory effects on tissue damage, inflammation and tumor growth. Previously, we showed that the cyano enone-containing 18βH-glycyrrhetinic acid derivative soloxolone methyl (SM) effectively suppressed the inflammatory response of macrophages in vitro and the development of influenza A-induced pneumonia and phlogogen-stimulated paw edema in vivo. In this work, we reported the synthesis of a novel 18βH-glycyrrhetinic acid derivative trioxolone methyl (TM), bearing a 2-cyano-3-oxo-1(2)-en moiety in ring A and a 12,19-dioxo-9(11),13(18)-dien moiety in rings C, D, and E. TM exhibited a high inhibitory effect on nitric oxide (II) production by lipopolysaccharide-stimulated J774 macrophages in vitro and dextran sulfate sodium (DSS)-induced colitis in mice, displaying higher anti-inflammatory activity in comparison with SM. TM effectively suppressed the DSS-induced epithelial damage and inflammatory infiltration of colon tissue, the hyperproduction of colonic neutral mucin and TNFα and increased glutathione synthesis. Our in silico analysis showed that Akt1, STAT3 and dopamine receptor D2 can be considered as mediators of the anti-colitic activity of TM. Our findings provided valuable information for a better understanding of the anti-inflammatory activity of cyano enone-bearing triterpenoids and revealed TM as a promising anti-inflammatory candidate.


2018 ◽  
Vol 16 ◽  
pp. 205873921876299 ◽  
Author(s):  
Donghui Cao ◽  
Jing Jiang ◽  
Dan Zhao ◽  
Menghui Wu ◽  
Houjun Zhang ◽  
...  

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for gastrointestinal diseases. Glycyrrhiza glabra, a traditional Chinese medicine, has been shown to safely suppress gastric cancer; however, the anti-inflammatory mechanisms in gastric tumorigenesis have been poorly investigated. Therefore, this study is committed to demonstrate the in vivo anti-inflammatory effect of 18β-glycyrrhetinic acid (GRA), the main active component of G. glabra. The lymphocytes and macrophages were heavily infiltrated in the transgenic mice that highly expressed cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1; however, a significant reduction was observed after treatment with GRA. In addition, GRA downregulated the protein levels of COX-2, GαS, EP2, and β-catenin, which were involved in the arachidonic acid pathway. In conclusion, our study showed the potential protective effects of GRA against inflammatory environment that might be involved in gastric tumorigenesis in vivo through the PGE2-EP2 receptor-mediated arachidonic acid pathway.


MedChemComm ◽  
2017 ◽  
Vol 8 (7) ◽  
pp. 1498-1504 ◽  
Author(s):  
Bo Li ◽  
Yongan Yang ◽  
Liuzeng Chen ◽  
Shichao Chen ◽  
Jing Zhang ◽  
...  

18α-GAMG exhibited strong anti-inflammatory activity through inhibiting the expression of iNOS, COX-2, and MAPKs, as well as activation of NF-κB.


Sign in / Sign up

Export Citation Format

Share Document