Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats

Aim of the study

Olive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified.

Materials and methods

All experiments were carried out on male Wistar rats. The tail-flick, hot-plate and formalin tests were used to assess the effect of OLE on nociceptive threshold. To determine the effect of OLE on analgesic and hyperalgesic effects of morphine, OLE (6, 12 and 25 mg/kg i.p.) that had no significant nociceptive effect, was injected concomitant with morphine (5 mg/kg and 1 μg/kg i.p., respectively). The tail-flick test was used to assess the effect of OLE on anti- and pro-nociceptive effects of morphine.

Results

The data showed that OLE (50-200 mg/kg i.p.) could produce dose-dependent analgesic effect on tail-flick and hot-plate tests. Administration of 200 mg/kg OLE (i.p.) caused significant decrease in pain responses in the first and the second phases of formalin test. In addition, OLE could potentiate the antinociceptive effect of 5 mg/kg morphine and block low-dose morphine-induced hyperalgesia.

Conclusion

Our results indicate that olive leaf extract has analgesic property in several models of pain and useful influence on morphine analgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions.     

Inhibitory effect of Thymus caramanicus Jalas on hyperglycemia-induced apoptosis in in vitro and in vivo models of diabetic neuropathic pain

Ethnopharmacological relevance

Since Thymus caramanicus Jalas is used as a folk medicine for the treatment of rheumatism, skin disorders, bacterial infections and diabetes and it contain antioxidant agents, we decided to investigate the possible effects of Thymus caramanicus Jalas (TCJ) extract on in vitro and in vivo models of diabetic neuropathy.

Materials and methods

The high glucose-induced cell injury in Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick and rotarod treadmill assessments were used to determine nociceptive threshold and motor coordination. Cell viability was determined by MTT assay test. Western blotting was performed to measurement of apoptosis markers.

Results

The data showed that elevation of glucose consecutively increases functional cell injury and apoptosis. Furthermore, diabetic rats developed thermal hyperalgesia and motor deficit. Activated caspase 3, cytochrome c release and Bax/Bcl-2 ratio were significantly increased in high glucose-treated PC12 cells and in spinal cord of diabetic animals. TCJ extract (60 and 80 µg/ml) attenuates high glucose-induced PC12 cells damage and apoptosis. In diabetic animals, TCJ extract at daily doses of 100 and 150 mg/kg ameliorated hyperalgesia and suppressed spinal apoptosis.

Conclusion

The data indicate that TCJ extract has neuroprotective effects against high glucose-induced neural damage. These protective effects are mediated, at least in part, through attenuation of neural apoptosis and suggest therapeutic potential of TCJ extract in amelioration of diabetic neuropathy.     

Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins

Hypertension is a harmful disease factor that develops unnoticed over time. The treatment of hypertension is aimed at an early diagnosis followed by adequate lifestyle changes rather than pharmacological treatment. The olive leaf extract EFLA943, having antihypertensive actions in rats, was tested as a food supplement in an open study including 40 borderline hypertensive monozygotic twins. Twins of each pair were assigned to different groups receiving 500 or 1000 mg/day EFLA943 for 8 weeks, or advice on a favourable lifestyle. Body weight, heart rate, blood pressure, glucose and lipids were measured fortnightly. Blood pressure changed significantly within pairs, depending on the dose, with mean systolic differences of < or =6 mmHg (500 mg vs control) and < or =13 mmHg (1000 vs 500 mg), and diastolic differences of < or =5 mmHg. After 8 weeks, mean blood pressure remained unchanged from baseline in controls (systolic/diastolic: 133 +/- 5/77 +/- 6 vs 135 +/- 11/80 +/- 7 mmHg) and the low-dose group (136 +/- 7/77 +/- 7 vs 133 +/- 10/76 +/- 7), but had significantly decreased for the high dose group (137 +/- 10/80 +/- 10 vs 126 +/- 9/76 +/- 6). Cholesterol levels decreased for all treatments with significant dose-dependent within-pair differences for LDL-cholesterol. None of the other parameters showed significant changes or consistent trends. Concluding, the study confirmed the antihypertensive and cholesterol-lowering action of EFLA943 in humans.     

The methanolic extract of Boesenbergia rotunda (L.) Mansf. and its major compound pinostrobin induces anti-ulcerogenic property in vivo: possible involvement of indirect antioxidant action

Ethnopharmacological relevance

Boesenbergia rotunda (L) Mansf. has been used for the treatment of gastrointestinal disorders including peptic ulcer. In the current study we aimed to investiagte the anti-ulcer activities of methanolic extract of B. rotunda (MEBR) and its main active compound, pinostrobin on ethanol-induced ulcer in rats. The possible involevement of lipid peroxidation, nitric oxide, cyclooxygenases and free radical scavenging mechanisms also has been investigated.

Materials and methods

Pinostrobin was isolated form the rhizomes of B. rotunda. Ulcer index, gastric juice acidity, mucus content, gross and histological gastric lesions and thiobarbituric acid reactive substances (TBARS) were evaluated in ethanol-induced ulcer in vivo. The effect of pinostrobin into lipopolysaccharide/interferon-γ stimulated rodent cells, COX-1 and COX-2 activities were done in vitro.

Results

Pre-treatment with MEBR, pinostrobin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of submucosal edema and leucocytes infiltration. Pinostrobin significantly (p<0.05) lowered the elevated TBARS level into gasteric homogenate. Pinostrobin did not produced significant in vitro inhibition of NO from LPS/IFN-γ activated rodent cells without affecting the viability of these cells. Further, the compound did bot revleaed inhibitory effects on both COX- 1& 2 enzymes. The antioxidant assays also exhibited non significance in vitro.

Conclusion

Thus it can be concluded that MEBR possesses anti-ulcer activity, which could be attributed to indirect anti-oxidant mechanism of pinostrobin but not to the intervention with nitric oxide and COX inflammation pathways.