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Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/Osteoarthritis Model by Suppressing Inflammation

Che Ahmad Tantowi NA, Lau SF, Mohamed S

Calcif. Tissue Int., 2018 10;103(4):388-399.
PMID: 29808374 DOI: 10.1007/s00223-018-0433-1

Osteoporosis (OP) and osteoarthritis (OA) are debilitating musculoskeletal diseases of the elderly. Ficus deltoidea (FD) or mistletoe fig, a medicinal plant, was pre-clinically evaluated against OP- and OA-related bone alterations, in postmenopausal OA rat model. Thirty twelfth-week-old female rats were divided into groups (n = 6). Four groups were bilateral ovariectomized (OVX) and OA-induced by intra-articular monosodium iodoacetate (MIA) injection into the right knee joints. The Sham control and OVX-OA non-treated groups were given deionized water. The three other OVX-OA groups were orally administered daily with FD extract (200, 400 mg/kg) or diclofenac (5 mg/kg) for 4 weeks. The rats' bones and blood were evaluated for protein and mRNA expressions of osteoporosis and inflammatory indicators, and micro-CT computed tomography for bone microstructure. The non-treated OVX-OA rats developed severe OP bone loss and bone microstructural damage in the subchondral and metaphyseal regions, supported by reduced serum bone formation markers (osteocalcin, osteoprotegerin) and increased bone resorption markers (RANKL and CTX-I). The FD extract significantly (p
Mistletoe fig (Ficus deltoidea Jack) leaf extract prevented postmenopausal osteoarthritis by attenuating inflammation and cartilage degradation in rat model

Che Ahmad Tantowi NA, Hussin P, Lau SF, Mohamed S

Menopause, 2017 Sep;24(9):1071-1080.
PMID: 28640163 DOI: 10.1097/GME.0000000000000882

OBJECTIVE: Ficus deltoidea Jack (mistletoe fig) is an ornamental plant found in various parts of the world and used as traditional herbal medicine in some countries. This study investigated the potential use of F deltoidea leaf extract to mitigate osteoarthritis (OA) in ovariectomized (estrogen-deficient postmenopausal model) rats and the mechanisms involved. Diclofenac was used for comparison.
METHODS: Sprague-Dawley female rats (12 weeks old) were divided randomly into five groups (n = 6): healthy; nontreated OA; OA + diclofenac (5 mg/kg); OA + extract (200 mg/kg); and OA + extract (400 mg/kg). Two weeks after bilaterally ovariectomy, OA was induced by intra-articular injection of monosodium iodoacetate into the right knee joints. After 28 days of treatment, the rats were evaluated for knee OA via physical (radiological and histological observations), biochemical, enzyme-linked immunosorbent assay, and gene expression analysis, for inflammation and cartilage degradation biomarkers.
RESULTS: The osteoarthritic rats treated with the extract, and diclofenac showed significant reduction of cartilage erosion (via radiological, macroscopic, and histological images) compared with untreated osteoarthritic rats. The elevated serum interleukin-1β, prostaglandin E2, and C-telopeptide type II collagen levels in osteoarthritic rats were significantly reduced by F deltoidea leaf extract comparable to diclofenac. The extract significantly down-regulated the interleukin-1β, prostaglandin E2 receptor, and matrix metalloproteinase-1 mRNA expressions in the osteoarthritic cartilages, similar to diclofenac.
CONCLUSIONS: F deltoidea leaf extract mitigated postmenopausal osteoarthritic joint destruction by inhibiting inflammation and cartilage degradation enzymes, at an effective extract dose equivalent to about 60 mg/kg for humans. The main bioactive compounds are probably the antioxidative flavonoids vitexin and isovitexin.
Epicatechin and scopoletin rich Morinda citrifolia (Noni) leaf extract supplementation, mitigated Osteoarthritis via anti-inflammatory, anti-oxidative, and anti-protease pathways

Wan Osman WN, Che Ahmad Tantowi NA, Lau SF, Mohamed S

J Food Biochem, 2019 03;43(3):e12755.
PMID: 31353568 DOI: 10.1111/jfbc.12755

The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia L. (MC) Noni leaves are non-toxic (unlike the fruits) and consumed as vegetables. The anti-osteoarthritis effects of the MC leaf extract against joint cartilage degradation and inflammation were investigated through cartilage explant cultures and pre-clinical animal study. Osteoarthritis were induced by intra-articular monosodium iodoacetate injection into the right knee. The extract, scopoletin and epicatechin, suppressed glycosaminoglycan and nitric oxide release from the cartilage explant in the presence of Interleukin-1β. After 28 days, the extract treatment reduced the in vivo serum levels and joint tissues mRNA expressions for joint cartilage degradation, aggrecanase, and collagenase biomarkers. The extract increased the bone formation marker PINP levels, besides improving the articular cartilage structure and chondrocytes cellularity. The extract improved bone formation/repair, subchondral bone structure, strength and integrity, as well as cartilage synthesis by suppressing inflammation, nitric oxide production, joint catabolism by proteases, and oxidative stress. PRACTICAL APPLICATIONS: The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia (Noni) leaves may be used as vegetables, functional food ingredient, or dietary supplements to suppress osteoarthritis progression against joint cartilage degradation and inflammation. The extract, scopoletin, or epicatechin, suppressed glycosaminoglycan, and nitric oxide release from the cartilage. The Morinda citrifolia leaf extract suppressed inflammation, nitric oxide production, tissues catabolism by proteases and oxidative stress to help reduce joint cartilage degradation, besides improving the articular cartilage structure, chondrocytes health, subchondral bone structure, bone formation/repair, and cartilage synthesis.
Labisia pumila prevented osteoarthritis cartilage degeneration by attenuating joint inflammation and collagen breakdown in postmenopausal rat model

Madzuki IN, Lau SF, Che Ahmad Tantowi NA, Mohd Ishak NI, Mohamed S

Inflammopharmacology, 2018 Oct;26(5):1207-1217.
PMID: 29460078 DOI: 10.1007/s10787-018-0452-6

The tropical herb Labisia pumila is traditionally used in facilitating childbirth and post-partum care. The effects of L. pumila leaf extract (LP) in explant cartilage culture and on postmenopausal osteoarthritis (OA) rat model were assessed. The LP (10, 25 and 50 µg/ml) or diclofenac (10 µg/ml) was added to the cartilage explants containing bovine IL-1β (20 ng/ml), to evaluate their direct effects on cartilage degradation. In the preclinical study, rats were grouped (n = 8) into: non-treated OA; OA + diclofenac (5 mg/kg); OA + LP extract (150 and 300 mg/kg); and healthy control. To induce OA, monosodium iodoacetate was injected into the ovariectomised female rats' intra-articular knee joints and evaluated for OA severity after 8 weeks via physical (radiological, macroscopic and histological observations), biochemical, ELISA and mRNA expression analysis (for inflammation and cartilage degradation biomarkers). The LP reduced the nitric oxide and proteoglycan release from the cartilage explants under IL-1β induction. The radiological, macroscopic, microscopic and histological images showed the OA rats treated with LP and diclofenac had significantly reduced osteophytes and cartilage erosions compared to non-treated OA rats. The extract significantly up-regulated the anti-inflammatory interleukin-10, collagen type II and down-regulated pro-inflammatory PTGS2 (prostaglandin-endoperoxide synthase 2) mRNA expressions compared to non-treated control. The LP treatment significantly reduced serum collagenases (MMP-1 and MMP-3) and collagen type II degradation biomarker (CTX-II) levels in OA rats. The LP containing myricetin and gallic acid suppressed inflammation, collagenases and cartilage degradation, and helped cartilage matrix synthesis, to prevent OA at the dose equivalent to 30-60 mg/kg daily for humans.