Muhammad Jahangir Hossen1, Sung Ho Jeon2, Seung Cheol Kim3, Ji Hye Kim4, Deok Jeong4, Nak Yoon Sung4, Sungjae Yang4, Kwang-Soo Baek4, Jun Ho Kim4, Deok Hyo Yoon5, Won O Song6, Kee Dong Yoon7, Sang-Ho Cho4, Sukchan Lee4, Jong-Hoon Kim8, Jae Youl Cho9. 1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Department of Animal Science, Patuakhali Science and Technology University, Bangladesh. 2. Department of Life Science Hallym University, Chuncheon 200-702, Republic of Korea. 3. Division of Gynecologic Oncology Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital College of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea. 4. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. 5. Department of Biochemistry, Kangwon National University, Chuncheon 220-700, Republic of Korea. 6. Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA. 7. College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Republic of Korea. 8. Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jhkim1@chonbuk.ac.kr. 9. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jaecho@skku.edu.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus acidus (L.) Skeels (Phyllanthaceae) has traditionally been used to treat gastric trouble, rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Despite this widespread use, the pharmacological activities of this plant and their molecular mechanisms are poorly understood. Therefore, we evaluated the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Pa-ME) and validated its pharmacological targets. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-treated macrophages, an HCl/EtOH-induced gastritis model, and an acetic acid-injected capillary permeability mouse model were employed to evaluate the anti-inflammatory activity of Pa-ME. Potentially active anti-inflammatory components of this extract were identified by HPLC. The molecular mechanisms of the anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. RESULTS: Pa-ME suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and prevented morphological changes in LPS-treated RAW264.7 cells. Moreover, both HCl/EtOH-induced gastric damage and acetic acid-triggered vascular permeability were restored by orally administered Pa-ME. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signalling events upstream of NF-κB translocation, such as phosphorylation of Src and Syk and formation of Src/Syk signalling complexes, were also inhibited by Pa-ME. The enzymatic activities of Src and Syk were also suppressed by Pa-ME. Moreover, Src-induced and Syk-induced luciferase activity and p85/Akt phosphorylation were also inhibited by Pa-ME. Of the identified flavonoids, kaempferol and quercetin were revealed as partially active anti-inflammatory components in Pa-ME. CONCLUSION: Pa-ME exerts anti-inflammatory activity in vitro and in vivo by suppressing Src, Syk, and their downstream transcription factor, NF-κB.
ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus acidus (L.) Skeels (Phyllanthaceae) has traditionally been used to treat gastric trouble, rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Despite this widespread use, the pharmacological activities of this plant and their molecular mechanisms are poorly understood. Therefore, we evaluated the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Pa-ME) and validated its pharmacological targets. MATERIALS AND METHODS:Lipopolysaccharide (LPS)-treated macrophages, an HCl/EtOH-induced gastritis model, and an acetic acid-injected capillary permeability mouse model were employed to evaluate the anti-inflammatory activity of Pa-ME. Potentially active anti-inflammatory components of this extract were identified by HPLC. The molecular mechanisms of the anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. RESULTS:Pa-ME suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and prevented morphological changes in LPS-treated RAW264.7 cells. Moreover, both HCl/EtOH-induced gastric damage and acetic acid-triggered vascular permeability were restored by orally administered Pa-ME. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signalling events upstream of NF-κB translocation, such as phosphorylation of Src and Syk and formation of Src/Syk signalling complexes, were also inhibited by Pa-ME. The enzymatic activities of Src and Syk were also suppressed by Pa-ME. Moreover, Src-induced and Syk-induced luciferase activity and p85/Akt phosphorylation were also inhibited by Pa-ME. Of the identified flavonoids, kaempferol and quercetin were revealed as partially active anti-inflammatory components in Pa-ME. CONCLUSION:Pa-ME exerts anti-inflammatory activity in vitro and in vivo by suppressing Src, Syk, and their downstream transcription factor, NF-κB.
Authors: Kon Kuk Shin; Jae Gwang Park; Yo Han Hong; Nur Aziz; Sang Hee Park; Sunggyu Kim; Eunji Kim; Jae Youl Cho Journal: Evid Based Complement Alternat Med Date: 2019-09-12 Impact factor: 2.629