| خلاصه مقاله | Opioids are potent analgesics but tolerance and physical addiction to them has limited their usage. Based on evidence from different studies of opioid tolerance we found that morphine improved the release of pro-inflammatory cytokines.
Since many years ago, natural products are prescribed for relieving and treatment of diseases. Marrubium vulgare is a perennial herb belonging to Lamiaceae family and is known as “horehound”.
Phytochemical analysis of M. vulgare showed the presence of alkaloids, steroids, flavonoids, tannins, phenylpropanoid esters and diterpenoids. M. vulgare is known for its remarkable diterpenoids; marrubiin and premarrubiin. A study demonstrated that steroids and terpenes of M.vulgare have anti-inflammatory and analgesic activities.
Object: The main purpose of our study was to elucidate the effect of M. vulgare on delaying morphine-induced tolerance for the first time.
Methods
Male Wistar rats were assigned to 6 groups(n=8) of morphine (10mg/kg, i.p), morphine (10mg/kg, i.p) in combination with three different doses of the extract (20, 40 and 80mg/kg, i.p) and morphine (10mg/kg, IP) in combination with vehicle (0.25ml/rat DMSO 50% in saline, i.p) and the last one received the effective dose of extract (80mg/kg, i.p) without morphine. Every other day nociception was examined using hotplate test (55±0.5 °C; cut-off time= 40sec). Then calculated MPE% related to the following equation:
MPE% = [(TL - BL) / (T cut-off - BL)] × 100
MPE= Maximum possible effect
TL = Test Latency time
BL = Base Latency time.
Results and Discussion
The morphine group became tolerant on day 7. There was no significant difference between the control group (morphine + vehicle) and the morphine group (p = 0.685). The groups were received the extract with doses 20,40 and 80 mg/kg had tolerance on days 9, 11, and 19 respectively. The group that received only 80 mg/kg extract had tolerance on day 3.
Flavonoids of M. vulgare inhibit the synthesis and activities of different pro-inflammatory mediators such as IL-1β, TNF-α, and IL-6. Also, glycosidic phenylpropanoid esters showed an inhibitory activity toward the Cox-2 enzyme (2). Moreover, β-sitosterol, marrubiin, and premarrubiin modulate the B2 receptors against bradykinin and prostaglandin receptors and have anti-inflammatory and analgesic activities. Opioid receptor desensitization occurs through phosphorylation by second messenger kinases such as protein kinase C (PKC). A phenylpropanoid ester of M. vulgare showed antioxidant activity by interfering with the PKC pathway.
Therefore, it could be proposed that these components of M. vulgare extract have the potential to delay morphine-induced tolerance.
Conclusion
Our results demonstrated that M. vulgare extract delayed morphine- induced tolerance. It seems that acute administration of M. vulgare decrease pro-inflammatory markers. Research about the pharmacology of natural products are essential to achieve evidence about the value of therapeutic plants in phytotherapy. Our experiments therefore illustrate evidence of the pharmacology of M. vulgare. |