Ceratonia siliqua L. (Leguminosae) has neuroprotective, mutagenic, hypotensive, anti-bacterial, hypoglycaemic, and anti-inflammatory effects through extracts from its leaves. Therefore, the aim of this study is to assess the anti-nociceptive activity of ethanol extracts of Ceratonia siliqua leaves. Ethanol extract of Ceratonia siliqua leaves were studied using well-established animal models of inflammation and pain. A hot plate latency assay (55 °C) was used to assess the analgesic effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extracts in addition to paw licking time in early and late phase using a formalin-induced paw licking assay test. Paw oedema induction using carrageenan and cotton pellet granuloma assays were used to assess the anti-inflammatory effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extract. The ethanol extract of Ceratonia siliqua leaves reduces paw licking time in early and late phase after formalin injection. The same effect was also observed when the hotplate test was performed. Ethanol extract of Ceratonia siliqua leaves caused dose dependent inhibition in paw oedema after the injection of carrageenan and cotton pellet granuloma in mice. These effects were not antagonized when opioid receptors were blocked by naloxone (5 mg/kg). The preliminary phytochemical analysis of the ethanol extract of Ceratonia siliqua leaves showed the presence of tannins, alkaloids, flavonoids and terpenoids. The present data indicate that ethanol extract of Ceratonia siliqua leaves might possess anti-inflammatory and anti-nociception properties and should be considered for further therapeutic research.

Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 (p < 0.01 and p < 0.05, respectively) and pAMPK-α1 (p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver (p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls (p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.