Comparison of diclofenac with apigenin-glycosides rich Clinacanthus nutans extract for amending inflammation and catabolic protease regulations in osteoporotic-osteoarthritis rat model

Daru. 2020 Dec;28(2):443-453. doi: 10.1007/s40199-020-00343-y. Epub 2020 May 9.

Abstract

Background: Osteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged.

Objectives: The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats.

Methods: Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes.

Results: HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac.

Conclusion: This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract.

Keywords: Anti-inflammatory; Apigenin-C-glycosides; Osteoarthritis; Osteoporosis.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Apigenin / chemistry
  • Cytokines / genetics
  • Diclofenac / administration & dosage*
  • Diclofenac / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / drug effects
  • Glycosides / administration & dosage*
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Iodoacetic Acid / adverse effects
  • Lamiaceae / chemistry*
  • Matrix Metalloproteinase 13 / genetics*
  • Matrix Metalloproteinase 13 / metabolism
  • Osteoarthritis / chemically induced
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoporosis / drug therapy*
  • Osteoporosis / etiology
  • Osteoporosis / genetics
  • Osteoporosis / metabolism
  • Ovariectomy / adverse effects
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cytokines
  • Glycosides
  • Plant Extracts
  • Diclofenac
  • Apigenin
  • Matrix Metalloproteinase 13
  • Mmp13 protein, rat
  • Iodoacetic Acid