Unraveling the Potential of Isorhamnetin as an Adjuvant in Depression Treatment with Escitalopram.

Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model.

Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.

About anxiety levels and anti-anxiety drugs among quarantined undergraduate Jordanian students during COVID-19 pandemic.

OBJECTIVE: This study was conducted to study the anxiety scores among undergraduate university students in Jordan during COVID-19 pandemic and to assess the relationship between quarantine and shifting to distance learning resulted from the governmental strict isolation measures and severity of anxiety among students. METHODS: A cross-sectional design was conducted to meet the study objectives. A convenience sample of 736 undergraduate university students in Jordan was recruited, and anxiety was assessed using the Hamilton Anxiety Scale. RESULTS: The results indicated that anxiety score was 22.76 and 40.6% of the participant experienced moderate to severe anxiety, whereas 23.5% experienced mild to moderate anxiety and 35.9% experienced mild anxiety. Factors like suffering from chronic illnesses, having chronic medications, grade point average, shifting to distance learning, quarantine during the pandemic, study duties, the newly developed evaluation methods and the experience of students towards the use of anti-anxiety drugs and herbs had significantly increased the anxiety scores. CONCLUSION: Our findings indicate that quarantine and shifting to distance learning during COVID-19 pandemic have negatively affected the anxiety scores of the university students which should be taken in consideration by the policymakers in Jordan in order to support this vulnerable group.

Lysionotin exerts antinociceptive effects in various models of nociception induction.

Background: Lysionotin, a natural flavonoid extracted from Lysionotus pauciflorus Maxim (Gesneriaceae), has several pharmacological effects including anti-bacterial, anti-hypertensive and anti-inflammatory effects. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of lysionotin using chemically and thermally induced nociception in a mouse model. Methods: The antinociceptive effects of various lysionotin doses (50, 100, 150, and 200 µg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin- and glutamate-induced paw licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results: Lysionotin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 60% inhibition at a dose of 200 µg/kg. Lysionotin also caused a significant increase in the latency period in response to the hot plate test (76.4% at 200 µg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw licking test. Naloxone significantly reverses the effect of lysionotin in both hot plate test and formalin-induced paw licking test. Moreover, lysionotin significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57% and 67.2%, respectively at a dose of 200 µg/kg). Thus, lysionotin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system. Conclusion: Lysionotin possesses antinociceptive activity on adult mice that is mediated through both central and peripheral pathways.

New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound.

2',3,3,5'-Tetramethyl-4'-nitro-2'H-1,3'-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB 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 TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p < 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p < 0.001), and increased GSH level (p < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.

Erratum to "Ceratonia siliqua leaves ethanol extracts exert anti-nociceptive and anti-inflammatory effects" [Heliyon 8 (8), (August 2022) Article e10400].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10400.].

Ceratonia siliqua leaves ethanol extracts exert anti-nociceptive and anti-inflammatory effects.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts.

CONTEXT: The leaf of sage Salvia officinalis L. (Lamiaceae) is reputed in the folk medicine of Arabia, and Jordan in particular, to relieve pain associated with gastrointestinal disturbance. OBJECTIVES: Evaluation of the antinociceptive and anti-inflammatory activities of aqueous and butanol extracts of S. officinalis leaf. MATERIALS AND METHODS: The analgesic effects of the aqueous extract (10, 31.6, 100, 316, 1000 mg/kg) and butanol extract (10, 31.6, 100, 316 mg/kg) were studied using the hot-plate test for mice and the formalin-induced paw licking in rats. The effects were compared to those of morphine and the influence of naloxone on these effects was also evaluated. The same concentrations of both extracts were used to evaluate their anti-inflammatory effects using the cotton pellet granuloma and carrageenan-induced paw edema in rats. RESULTS: The aqueous extract (10, 31.6, 100, 316, 1000 mg/kg) and butanol extract (10, 31.6, 100, 316 mg/kg) caused analgesic effect in the hot-plate latency assay as well as in early and late phases of formalin-induced paw licking in rats. These effects were reduced by the opioid receptor antagonist, naloxone (5 mg/kg). The same range of doses of both extracts caused dose-dependent inhibition of carrageenan-induced paw edema in rats as well as inhibition of cotton pellet granuloma. DISCUSSION AND CONCLUSION: These observations suggest that the sage leaf aqueous and butanol extracts have analgesic and anti-inflammatory effects, confirming the traditional use of this plant for pain alleviation.

Antidiarrheal activity of Laurus nobilis L. leaf extract in rats.

In Jordan, the leaves of Laurus nobilis (Family Lauraceae) have been used in folk medicine for the treatment of diarrhea, among other ailments. However, the ethnopharmacology of this plant needs to be scientifically validated. The present work was carried out to evaluate the scientific basis of the antidiarrheal effect of the aqueous extract of L. nobilis leaf. L. nobilis leaf extract significantly inhibited castor oil-induced diarrhea (effective concentration producing 50% of the maximum response [EC(50)]=150±6.4 mg/kg) and reduced castor oil-induced enteropooling in rats (EC(50)=162±5.9 mg/kg). The extract also significantly inhibited intestinal transit of a charcoal meal and exerted a significant dose-dependent relaxation (EC(50)=71±5.3 mg/mL) on rat ileal smooth muscle. The aqueous extract tested positive for flavonoids, alkaloids, and tannins. These results established the efficacy of L. nobilis leaf aqueous extract as an antidiarrheal agent and are consistent with the popular use of the plant in the treatment of gastrointestinal disorders, particularly diarrhea.