Trans-cinnamaldehyde (TCA), a natural cinnamaldehyde derivative of cinnamon oil, is known for anti-inflammatory, anti-bacterial, anti-fungal, anti-diabetic, and anti-cancer activities. However, no study has examined the protective mechanisms of TCA on complete Freund’s adjuvant (CFA)-induced arthritis. Chronic arthritis was induced in mice by triple dose injection of 0.1 ml CFA in the first two days, then a treatment with TCA (100 mg/kg, i.p.) and the anti-arthritic drug; methotrexate (MTX, 0.75 mg/kg, i.p., 3 times/week) started from day 10 after CFA and continued till day 35.TCA ameliorated the CFA-induced arthritis features, indicated by the decrease in serum rheumatoid factor, paw swelling, arthritis index and the arthritis changes in limb histology. Additionally, TCA treatment showed anti-inflammatory actions through downregulation of TNF-α, NF-κB and COX-2 expressions and marked reduction in IL-1β, IL-6, IL-23 and IL-17 levels in inflamed paw tissues.Consequently, TCA can decrease arthritis progression and inhibit the immune/inflammatory responses initiated by TNF-α/IL-1β/IL-6/IL-23/IL-17 signals, via NF-κB modulation, almost to the same extent accomplished by MTX. Therefore, TCA could be a promising anti-arthritic drug.

The current work explored the influences of time dependent Sildenafil (SILD) administration, and the possible outcomes from its concomitant administration with dexamethasone against acetic acid-induced ulcerative colitis in rats. Rats were assigned into six random groups: diseased group (AA), injected once with 2 ml acetic acid (3%) intrarectally, 2 days before sacrification. SILD + AA, received sildenafil (25 mg/kg, orally) for 6 days starting 3 days pre-injection of AA; SILD-t + AA, received sildenafil (25 mg/kg, orally), starting at time of AA injection and continued for 3 days; DEXA + AA, received dexamethasone (2 mg/kg, i.p.) for 3 days, starting at time of AA injection; SILD-t + DEXA + AA, received sildenafil (25 mg/kg, orally) and dexamethasone (2 mg/kg, i.p.), as mentioned. Sildenafil markedly ameliorated disease activity index (DAI), ulcer scores, colon length shortening and colonic histopathological changes. Mechanistically, Sildenafil markedly attenuated immunoexpression of NF-κB p65/ TNF-α and COX-2, diminished oxidative stress (↓ MDA/NO levels and ↑ GSH level and SOD activity), increased levels of Nrf-2/HO-1, compared to untreated group. Taken together, Sildenafil treatment suppressed acetic acid-induced ulcerative colitis, probably via inhibiting NF-κB/TNF-α signaling dependent of Nrf-2/HO-1 pathway, reducing oxidative stress and attenuating inflammation. Surprisingly, effects of sildenafil were unpromoted in a time dependant manner. Short term treatment with sildenafil was sufficient to exert its coloprotective effect, while longer term pretreatment was only superior among other treatments in the macroscopical changes. Moreover, concurrent administration of sildenafil and dexamethasone had the preference in boosting the antioxidant defense and anti-inflammatory mechanisms, visualized by histopathological/immunohistochemical changes.

Wound healing comprises organized events involving tissue repair and regeneration. The discovery of toll-like receptors (TLRs) sheds recent light on the mechanisms involved in initiating inflammatory responses throughout the healing cascades. Hibiscus sabdariffa (HS) components may exhibit a wound healing action, owing to their antioxidant and anti-inflammatory activities. This study was designed to investigate the early effects of HS loaded in an ointment base on wound healing, antioxidant, antimicrobial effects, burning intensity, and histopathological features on the rat burn model in comparison to the standard treatment, Iruxol^® ointment. A burn injury model was used to evaluate the wound healing potency of the preparation. Rats were treated with ointments three times on the day of the induction of the burn. Findings revealed that the strong antioxidant properties of the HS-loaded ointment augmented the skin healing potential by stimulating biomarkers required for skin regeneration. HS repressed the burning-induced inflammation by the effective reduction in the levels of tumor necrosis factor α (TNF-α) and IL-6 through TLR4 protein inhibition. Topical HS downregulates transforming growth factor-beta (TGF-β) levels. HS extract possesses a potential bactericidal activity against highly resistant clinical isolates of Pseudomonas aeruginosa. Overall, this study proclaims that HS-loaded topical preparations could be a valuable product that serves as adjuvants to accelerate burn wound healing through inactivating the TLR4 pathway.

Objectives: Rhabdomyolysis-associated acute kidney injury (AKI) is a manifestation frequently observed in many cases. Sildenafil (Sild) is a phosphodiesterase-5 inhibitor selected in this study for its experimental protective effects in muscle and kidney injury experimental models. The current study aimed to hypothesize that Sild had a renoprotective effect through the anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in glycerol (Gly)-induced rhabdomyolysis rat model. Methods: Male Sprague Dawley rats were allocated into four groups: control group (saline, i.p); Sild control group (5 mg/kg, orally); glycerol (Gly) group (50%, 10 ml/kg, i.m.); prophylactic Sild plus glycerol group (5 mg/kg, orally, 1 hr before glycerol). All treatments were applied as a single dose. Blood samples and renal tissues were collected 24 hr following glycerol injection. Results: Gly produced renal morphological changes, muscle, and renal dysfunction, in addition to increased mortality rates, oxidative stress, renal inflammatory responses, and renal apoptosis. Sild reduced muscle/kidney function disturbances (serum total CK, CK-MB, creatinine, BUN, in addition to urinary creatinine levels), reduced oxidative stress in renal tissue, increased antioxidant defense (TAC, SOD, NRF-2/HO-1), decreased mortality rates, and accelerated renal histological recovery. Additionally, inflammatory mediator levels of TNF-α, NF-κB, and COX-2 were suppressed. Moreover, the study revealed new insights into protection from rhabdomyolysis-associated AKI, through reduction of renal apoptosis by decreasing levels of BAX and increasing levels of BCL-2. Conclusions: Sild protected against rhabdomyolysis-linked renal morphological damage, renal and muscle function disturbances, by decreasing renal oxidative stress, inflammation, and apoptosis. Therefore, Sild proved its muscle/reno-protective impacts, and possibly can be used as a new therapeutic approach for acute muscle and kidney injuries, which represents a new benefit for a common and widely used medication.