Standardized Centella asiatica extract ECa 233 alleviates pain hypersensitivity by modulating P2X3 in trigeminal neuropathic pain

Abstract During oral surgery and temporomandibular joint repositioning, pain hypersensitivity often occurs due to irritation or inflammation of the nerve endings in the orofacial region. Objective: This study aimed to investigate the effects of ECa 233, a Centella asiatica-standardized extract, on the development of mechanical hyperalgesia and allodynia induced by chronic constriction injury of the infraorbital nerve in mice. Methodology: The right infraorbital nerves of the mice were ligated. Oral carbamazepine (20 mg/kg) or ECa 233 (30, 100, or 300 mg/kg) was administered daily for 21 days. Von Frey and air-puff tests were performed on both sides of the whisker pad on days 0, 7, 14, and 21. Thereafter, the expression of purinergic receptor subtype 3 (P2X3) and voltage-gated sodium channel 1.7 (NaV1.7), a transmembrane protein, in the trigeminal ganglion and c-fos immunoreactivity-positive neurons in the trigeminal nucleus caudalis was assessed. Results: After 21 days of infraorbital nerve ligation, the mice showed allodynia- and hyperalgesia-like behavior, P2X3 and NaV1.7 were upregulated in the trigeminal ganglion, and nociceptive activity increased in the trigeminal nucleus caudalis. However, the oral administration of carbamazepine (20 mg/kg), ECa 233 (100 mg/kg), or ECa 233 (300 mg/kg) mitigated these effects. Nevertheless, ECa 233 failed to affect NaV1.7 protein expression. Conclusion: Carbamazepine and ECa 233 can prevent pain hypersensitivity in mice. Considering the side effects of the long-term use of carbamazepine, ECa 233 monotherapy or combined ECa 233 and carbamazepine therapy can be used as an alternative for regulating the development of hypersensitivity in trigeminal pain. However, further detailed clinical studies should be conducted to provide comprehensive information on the use of ECa 233.

A standardized extract of Centella asiatica (ECa 233) prevents temporomandibular joint osteoarthritis by modulating the expression of local inflammatory mediators in mice

Abstract Objectives To investigate the effect of a standardized extract of Centella asiatica (ECa 233), which has anti-inflammatory properties, on the local expression of the transient receptor potential vanilloid 1 (TRPV1), the acid-sensing ion channel subunit 3 (ASIC3), and the calcitonin gene-related peptide (CGRP) in the temporomandibular joint (TMJ) structure 21 days after injecting the TMJ with complete Freund's adjuvant (CFA). Methodology A mouse model was induced by analyzing the CFA-injected TMJ on days 7, 14, and 21. We assessed TMJ histology by the osteoarthritis cartilage grade score. Then, we observed the effect of different ECa 233 concentrations (30, 100, and 300 mg/kg) and of 140 mg/kg ibuprofen doses on TRPV1, ASIC3, and CGRP local expression on day 21. Results Osteoarthritis cartilage scores were 1.17±0.37 and 3.83±0.68 on days 14 and 21, respectively, in the CFA group (n=5). On day 21, TRPV1, ASIC3, and CGRP expression significantly increased in the CFA group. In the ibuprofen-treated group, TRPV1 expression significantly decreased, but ASIC3 and CGRP showed no significant difference. All ECa 233 doses reduced TRPV1 expression, but the 100 mg/kg ECa 233 dose significantly decreased ASIC3 expression. Conclusions TRPV1, ASIC3, and CGRP expression increased in mice with TMJ-OA on day 21. All ECa 233 and ibuprofen doses inhibited pathogenesis by modulating the local expression of TRPV1 and ASIC3. Therefore, ECa 233 was more effective than ibuprofen.

Oxcarbazepine as add-on therapy in Thai epileptic patients with refractory partial seizures.

OBJECTIVES: To evaluate efficacy and safety of oxcarbazepine (OXC) as add-on therapy in Thai refractory epileptic patients. MATERIAL AND METHOD: A randomized, double-blind clinical trial was conducted in outpatients of the Epilepsy Clinic of Phramongkutklao Hospital. OXC in the doses of 600 or 1200 mg/d were added to 39 refractory epileptic patients with the median baseline seizure frequency of at least 2 per 28 days. RESULTS: Of 35 patients who completed the 98-day treatment period, 4 became seizure free. A reduction in median seizure frequency of 47% and 58% was observed in patients in the 600 and 1,200 mg OXC/d groups, respectively. Among them, 44% and 53% demonstrated > or = 50% reduction in median seizure frequency. About 85% of patients in each group reported one or more mild to moderate adverse events. CONCLUSION: OXC in the doses of 600 and 1200 mg/d appear to be safe and effective as adjunctive therapy in Thai refractory epileptic patients. Further studies are needed to confirm its long-term efficacy and tolerability.

Isobolographically additive anticonvulsant activity between Centella asiatica's ethyl acetate fraction and some antiepileptic drugs.

OBJECTIVE: To investigate interaction between orally given Centella asiatica's ethyl acetate fraction (EACA) and intraperitoneally administered antiepileptic drugs (AEDs), namely, phenytoin, valproate and gabapentin. MATERIAL AND METHOD: Isobolographic analysis was used to evaluate the interaction between EACA and AEDs in terms of protection of mice in the pentylenetetrazole test. Rotarod test was used to evaluate neurotoxicity. RESULTS: When given alone, the median effective dose of phenytoin, valproate and gabapentin were found to be 13, 104, and 310 mg/kg BW, respectively, whereas the corresponding values in the presence of EACA were 5, 29 and 79 mg/kg BW. Together with isobolographic analysis, the results obtained indicated an additive effect among all combinations tested. In relation to neurotoxicity, combination of gabapentin and EACA demonstrated a broader margin between the effective dose and the neurotoxic dose while the other two combinations did not. CONCLUSION: The present finding suggested a potential of Centella asiatica to be developed as an adjunctive medication for epileptic patients.