Rashmi Rekha Kumari

Effect of iNOS inhibitor S-methylisothiourea in monosodium iodoacetate-induced osteoathritic pain: Implication for osteoarthritis therapy

Much information is available on the role of nitric oxide (NO) in osteoarthritis (OA). However, its role has not been studied in the monosodium iodoacetate (MIA)-induced model of osteoarthritic pain. The present study was undertaken in rats to investigate the effect of iNOS inhibitor S-methylisothiourea (SMT) in MIA-induced osteoathritic pain and disease progression in rats. Osteoarthritis was produced by single intra-articular injection of the MIA in the right knee joint on day 0. Treatment groups were orally gavazed with different doses of SMT (10, 30 and 100mg/kg) and etoricoxib (10mg/kg) daily for 21 days. On days 0, 3, 7, 14 and 21, pain was measured and histopathology of right knee joint was done on day 21. SMT produced analgesia in a dose-dependent manner as shown by mechanical, heat hyperalgesia, knee vocalization, knee squeeze test, and spontaneous motor activity test. SMT reduced NO production in synovial fluid. Histopathological findings indicated that SMT reduced disease progression as evident from complete cartilage formation in rats treated with SMT at 30 mg/kg. In conclusion, the results indicate that SMT attenuates the MIA-induced pain and histopathological changes in the knee joint. The antinociceptive and antiarthritic effects of SMT were mediated by inhibiting cartilage damage and suppression of NO in synovial fluid. It is suggested that SMT has potential as a therapeutic modality in the treatment of osteoarthritis.

Chondroprotective and anti‐inflammatory effects of S‐methylisothiourea, an inducible nitric oxide synthase inhibitor in cartilage and synovial explants model of osteoarthritis

To study the chondroprotective and anti‐inflammatory potential of inducible nitric oxide synthase (iNOS) inhibitor S‐methylisothiourea (SMT) in in‐vitro model.

Effect of S-methylisothiourea, an inducible nitric oxide synthase inhibitor, in joint pain and pathology in surgically induced model of osteoarthritis.

Abstract The aim of the present study was to evaluate in vivo modulatory effect of S-methylisothiourea (SMT), a preferential inhibitor of inducible nitric oxide synthase (iNOS) on pain and pathology in the surgical model of osteoarthritis (OA) in rats. The OA was produced by the anterior cruciate ligament transection (ACLT) and medial meniscectomy (MMx) of right knee. SMT was administered 1 day prior to the production of OA and continued up to day 42 postoperation. Mechanical hyperalgesia, thermal hyperalgesia, tail flick latency after repeated flexion and extension of OA knee and knee diameter of right knee were determined at weekly intervals. Serum levels of IL-1β, TNF-α and nitrite concentration were determined at the end of the experiment. Glycosaminoglycan (GAG) content, collagen content and histopathological evaluation of articular cartilage were also determined at the end of the experiment. SMT reduced mechanical hyperalgesia and the serum levels of IL-1β, TNF-α and nitrite. Further, SMT reduced the loss of GAG from articular cartilage. Microscopically, SMT reduced the severity of the cartilage lesion. The results indicate the effectiveness of SMT in attenuating the pain and pathology of experimental OA phase by reducing the production of nitric oxide and interleukin-1β and tumor necrosis factor-α, which are known to play a major role in the pathophysiology of OA.

Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats

Background & objectives: Osteoarthritis (OA) is a degenerative disease characterized by joint pain and progressive loss of articular cartilage. Entada pursaetha has been traditionally used in the treatment of inflammatory disease, liver ailment, etc. In this study we investigated suppressive effect of ethanolic extract of E. pursaetha (EPE) on monosodium iodoacetate (MIA)-induced osteoarthritis pain and disease progression by histopathological changes in joints in a rat model. Methods: OA was induced in right knee of rat by intra-articular injection of 3 mg of MIA and characterized by pathological progression of disease and pain of affected joint. Spontaneous movements, mechanical, thermal and cold sensitivity were monitored at days 0 (before drug and MIA injection), 7, 14 and 21 of MIA administration. EPE (30, 100 and 300 mg/kg), vehicle or etoricoxib (10 mg/kg; reference drug) were administered daily for 21 days by oral route. Results: EPE at various doses significantly reduced mechanical, heat, cold hyperalgesia and increased the horizontal and vertical movements in intra-articular MIA injected rats. EPE prevented the damage to cartilage structure and reduced the cellular abnormalities. Articular cartilage of rats treated with EPE at 300 mg/kg group was almost normal with well-developed smooth surface and chondrocytes were distributed individually or arranged in column. Interpretation & conclusions: The present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials.

Analgesic activity of Eugenia jambolana leave constituent: A dikaempferol rhamnopyranoside from ethyl acetate soluble fraction

Abstract Context: Eugenia jambolana Lam. (Myrtaceae) is a medicinal plant used in folk medicine for the treatment of diabetes, inflammation, and pain. Objective: We investigated the antinociceptive effect of kaempferol-7-O-α-l-rhamnopyranoside]- 4′-O-4′-[kaempferol-7-O-α-l-rhamnopyranoside (EJ-01), isolated from the E. jambolana leaves. Materials and methods: EJ-01 (3, 10, and 30 mg kg−1, orally) was assessed for peripheral (formalin-nociception and acetic acid-writhing) and central (hot plate and tail flick test) analgesic activity in mice and the in vitro anti-inflammatory activity (25, 50, and 100 µg mL−1) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Results and discussion: EJ-01 (10 and 30 mg kg−1) significantly inhibited mean writhing counts (37.74 and 36.83) in acetic acid writhing and paw licking time (55.16 and 45.66 s) in the late phase of the formalin test as compared with the respective control (60.66 and 104.33 s). EJ-01 did not show analgesic activity in central pain models. Significant reduction in the tumor necrosis factor (TNF)-α (295.48, 51.20, and 49.47 pg mL−1) and interleukin (IL)-1β (59.38, 20.08, and 15.46 pg mL−1) levels were observed in EJ-01-treated medium (25, 50, and 100 µg mL−1) as compared with vehicle-treated control values (788.67 and 161.77 pg mL−1), respectively. Significant reduction in total nitrite plus nitrate (NOx) levels (70.80 nmol) was observed in the EJ-01-treated medium (100 µg mL−1) as compared with the vehicle-treated value (110.41 nmol). Conclusion: EJ-01 is a valuable analgesic constituent of E. jambolana leaves and this study supports the pharmacological basis for the use of this plant in traditional medicine for curing inflammatory pain.