title: Diarylheptanoids from Alnus nepalensis attenuates LPS-induced inflammation in macrophages and endotoxic shock in mice.
abstract: Diarylheptanoids, a group of plant secondary metabolites are increasingly recognized as potential therapeutic agents. The aim of study was to ascertain the anti-inflammatory profile of diarylheptanoids from Alnus nepalensis against lipopolysaccharide (LPS)-induced inflammation in macrophages and endotoxic shock in mice. Extracts prepared from dried leaves of A. nepalensis using standard solvents were tested against LPS-induced inflammation in macrophages. Among all, butanol extract (ANB) has shown most significant inhibition of pro-inflammatory cytokines without any cytotoxicity. HPLC analysis of ANB showed the presence of diarylheptanoids. The diarylheptanoids were further isolated and tested in-vitro for anti-inflammatory activity. Treatment of isolated diarylheptanoids (HOG, ORE and PLS) was able to reduce the production and mRNA level of pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, we demonstrated that it inhibited the expression of NF-kB protein in LPS-induced inflammation in macrophages. In-vivo efficacy and safety profile of ANB revealed that oral treatment of ANB was able to improve the survival rate, and inhibited the production of pro-inflammatory cytokines in serum, attenuated vital organ injury in a dose dependent manner without any toxic effect at higher dose in mice. The results suggest that diarylheptanoids from A. nepalensis can be considered as potential therapeutic candidates for the management of inflammation related diseases.
authors.affiliation: Molecular Bioprospection Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Yadav
authors.affiliation: Molecular Bioprospection Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Maurya
authors.affiliation: Molecular Bioprospection Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Anant
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Molecular Bioprospection Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Madan M
authors.initials: MM
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, Indian Veterinary Research Institute, Izatnagar 243122, India.
authors.forename: Madhu C
authors.initials: MC
authors.lastname: Lingaraju
authors.affiliation: Department of Veterinary Medicine, Indian Veterinary Research Institute, Izatnagar 243122, India.
authors.forename: M I
authors.initials: MI
authors.lastname: Yatoo
authors.affiliation: Department of Pharmacology, Indian Veterinary Research Institute, Izatnagar 243122, India.
authors.forename: Uttam S
authors.initials: US
authors.lastname: Thakur
authors.affiliation: Molecular Bioprospection Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India. Electronic address: du.bawankule@cimap.res.in.
authors.forename: Dnyaneshwar U
authors.initials: DU
authors.lastname: Bawankule
mesh_terms: D029661:Alnus / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002460:Cell Line; D036381:Diarylheptanoids / Q000008:administration & dosage* / Q000302:isolation & purification; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts; D018515:Plant Leaves; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D036381:Diarylheptanoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha
keywords: Alnus nepalensis; Diarylheptanoids; Inflammation; Macrophages; Mice