Impact of Herbal Medicines like Nigella sativa, Trigonella foenum-graecum, and Ferula asafoetida, on Cytochrome P450 2C11 Gene Expression in Rat Liver.

AIM: Combined use of herbs and drugs may result in clinically important herb-drug interactions. The majorities of these interactions are thought to be metabolism-based and involve induction or inhibition of cytochrome P450 (CYP). The current study was designed to investigate the effect of some commonly used herbs on rat CYP2C11 gene expression and metabolic activity. METHODS: Wistar rats were treated for 7 days with increasing doses of 3 herbs; Nigella sativa, Trigonella foenum-graecum, and Ferula asafoetida. Thereafter, CYP2C11 mRNA and protein levels were determined by real-time polymerase chain reaction (RT-PCR) and western blot analyses, respectively. In vitro metabolic activity of CYP2C11 was performed on rat hepatic microsomes using tolbutamide as specific substrate. RESULTS: Our results showed that all the 3 herbs significantly inhibited the mRNA and protein expression levels of CYP2C11 in a dose-dependent manner. Furthermore, the in vitro enzyme metabolic activity study showed a significant decrease in the formation of 4-hyroxy-tolbutamide, a tolbutamide metabolite, at the higher doses. The inhibitory effects of the investigated herbs on rat CYP2C11 was in the order: Nigella Sativa > Trigonella foenum-graecum > Ferula asafoetida. CONCLUSIONS: The 3 herbs are strong inhibitor of CYP2C11 expression, which can lead to an undesirable pharmacological effect of clinically used CYP2C11 substrate drugs with a low therapeutic index.

Chemistry of spices: bornyl 4-methoxybenzoate from Ferula ovina (Boiss.) Boiss. (Apiaceae) induces hyperalgesia in mice.

UNLABELLED: Ferula ovina (Boiss.) Boiss. is a traditional Iranian flavoring agent used as an ingredient of spices and condiments. METHODS AND RESULTS: GC-MS analyses of F. ovina aerial parts' essential oil revealed the presence of a number of rare aromatic esters of monoterpenic alcohols. The structures of these esters were corroborated by synthesis, and one of them, bornyl 4-methoxybenzoate, turned out to be a new natural compound. The antinociceptive activities of the oil and the new ester were assessed in mice using several different laboratory models. The oil exerted strong peripheral and moderate central analgesic activities. Surprisingly, mice treated with bornyl 4-methoxybenzoate had an increased sensitivity to the noxious stimulus compared to that of the control group. A dynamic hot plate test was used to demonstrate that bornyl 4-methoxybenzoate induces hyperalgesia and not allodynia. CONCLUSION: Essential oil constituents impart this spice with both antinociceptive and hyperalgesic potentially flavor-related properties.

Role of ferutinin in the impairment of female sexual function induced by Ferula hermonis.

In the present study, we evaluated the effects of single components of Ferula hermonis extract on female rat sexual behaviour. Ovariectomized rats hormonally primed with estradiol benzoate (1.5 or 10 microg/rat s.c.) and progesterone (500 microg/rat s.c.) were acutely treated by oral gavage with ferutinin, teferin and teferdin (2.5 mg/kg). Thereafter they were tested for: a) partner preference, b) receptivity, c) proceptivity, d) paced mating behaviour. In the partner preference test, the choice of the female for a sexually active male was not influenced by the different treatments. Similarly, during the paced mating test, the contact-return latencies as well as the percentage of exits from the male compartment were not different in control and treated rats. Therefore none of the three compounds showed the capacity to alter sexual motivation. On the other hand, ferutinin, but not teferin and teferdin, significantly inhibited female receptivity. These results suggest a primary role of ferutinin in the impairment of sexual behaviour elicited by F. hermonis extract in hormone primed-female rats.

Fennel, cucumber, and melon allergy successfully treated with pollen-specific injection immunotherapy.

BACKGROUND: In subjects with both pollinosis and vegetable food allergy, most allergenic epitopes of fruits and vegetables are present in pollen. A recent study showed a marked reduction or a total disappearance of apple-induced oral allergy syndrome in patients receiving injection immunotherapy with birch pollen extracts. OBJECTIVE: To assess whether vegetable food allergy following other kinds of primary pollinosis may be successfully treated with pollen-specific immunotherapy. METHODS: A 34-year-old woman with long-standing pollinosis and typical oral allergy syndrome (OAS) with the ingestion of both fennel and cucumber and whose OAS was associated with immediate laryngeal edema after the ingestion of melon, was treated with two commercial depot aluminum hydroxide-adsorbed extracts of 1 grass pollen and 2 mugwort pollen 50% + ragweed pollen 50%. RESULTS: After 36 months of injection specific immunotherapy, the patient was able to tolerate both fresh fennel and cucumber without consequence on open oral challenge tests. After 43 months of immunotherapy, the patient tolerated fresh melon as well on open oral challenge. She has re-introduced these vegetables in her normal diet. Skin tests showed no reactivity to fresh fennel and there was a reduction of the wheal induced by fresh cucumber. CONCLUSION: Vegetable food allergy following primary sensitization to pollens, other than birch, may also be effectively reduced by pollen-specific injection immunotherapy.