Clinical and basic research of traditional Chinese medicine add-on treatment for drug-resistant epilepsy
Epilepsy, a serious health problem that affects people of all ages, races, and socioeconomic backgrounds, has a prevalence of 50 per 100 000 all around the world. Epilepsy is the second most common cause of mental health disability, particularly among young adults, and accounts for a worldwide burden of illness similar to that of breast cancer in women and lung cancer in men. The most common therapy of epilepsy are antiepileptic drugs. Most patients with epilepsy have a good prognosis and 50-60% of adults and children are expected to achieve seizure remission with medical management. Refractory epilepsy arises from a failure to achieve sustained seizure remission after trials of at least two, appropriately selected antiepileptic drug regimens that are tolerated at therapeutic dosages.
Recent years, new drugs and other therapies like surgery, ketogenic diet, vagus nerve stimulation are used in order to reduce seizures. However, it is still difficult to achieve the satisfied result.
Traditional Chinese herbal medicine Chaibei Zhixian decoction (CBZXD) consists of 7 Chinese herbs: Radix Bupleuri, Thunberg Fritillary Bulb, Rhizoma Pinellinae Praeparata, Acorus gramineus, lumbricus, Gastrodia Elata, concha ostreae Shellfish.
We have done the retrospective, self-controlled and randomized controlled trials[1] which showed that the Chaibei Zhixian Decoction add-on treatment for intractable epilepsy complex partial seizures has remarkable benefits in improving seizure frequency. Moreover, the efficacy is more prominent as the treatment course is prolonged, without any obvious adverse reactions. The Chaibei Zhixian Decoction add-on treatment for drug-resistant epilepsy is safe and effective. Meanwhile, we have undertaken 3 programs of Natural Science Foundation of China to explore the possible basic mechanisms of Chaibei Zhixian Decoction.
The efficacy of AEDs may be suspended by ATP binding cassette transporters at the blood–brain barrier resulting in a phenomenon of multi-drug resistance (MDR). MDR has been reported as one of the most important reasons for the occurrence of drug-resistance epilepsy. Among the ATP binding cassette transporters, P-glycoprotein (P-gp) was the first described and most extensively studied in drug-resistance epilepsy. The activity and expression of P-gp may exert a synergetic effect on the response of drug-resistance epilepsy to AEDs.
After administration, the seizure duration and grade of rats had a significant reduction. In contrast to the blank model group rats, the seizure duration and grade of rats in the intervention groups had a significant reduction with the combination of Chaibeizhixian decoction and carbamazepine showing the best effect.
The P-gp levels of were measured by western-blot analysis. PILO-induced epileptic seizures lead to significant increases of P-gp expression compared with the normal group. After the treatment of CBZXD and co-administration with CBZ for 3 months, the chronic epileptic rats got the markedly P-gp down-regulation in the hippocampus and cortex (CBZXD+CBZ group, CBZXD group). In contrast to the blank group rats, the rats with oral CBZ manifested a higher hippocampus and cortex P-gp expression.
Traditional Chinese herbal medicine prescription CBZXD and CBZ have a synergism effect on the PILO-induced chronic epilepsy. Its mechanism may be that CBZXD could reduce the expression of MDR1/ P-gp and then improve the concentration of CBZ in brain tissue of PILO -induced chronic epilepsy rats.
Jinmin Liu
The second clinical medical college of Beijing University of Chinese Medicine (BUCM)