Standardized Centella asiatica (ECa 233) extract decreased pain hypersensitivity development in a male mouse model of chronic inflammatory temporomandibular disorder.

Chronic inflammatory temporomandibular disorder (TMD) pain has a high prevalence, and available nonspecific treatments have adverse side effects. ECa 233, a standardized Centella asiatica extract, is highly anti-inflammatory and safe. We investigated its therapeutic effects by injecting complete Freund's adjuvant (CFA) into right temporomandibular joint of mice and administering either ibuprofen or ECa 233 (30, 100, and 300 mg/kg) for 28 days. Inflammatory and nociceptive markers, bone density, and pain hypersensitivity were examined. CFA decreased ipsilateral bone density, suggesting inflammation localization, which ipsilaterally caused immediate calcitonin gene-related peptide elevation in the trigeminal ganglia (TG) and trigeminal subnucleus caudalis (TNC), followed by late increase of NaV1.7 in TG and of p-CREB and activation of microglia in TNC. Contralaterally, only p-CREB and activated microglia in TNC showed delayed increase. Pain hypersensitivity, which developed early ipsilaterally, but late contralaterally, was reduced by ibuprofen and ECa 233 (30 or 100 mg/kg). However, ibuprofen and only 100-mg/kg ECa 233 effectively mitigated marker elevation. This suggests 30-mg/kg ECa 233 was antinociceptive, whereas 100-mg/kg ECa 233 was both anti-inflammatory and antinociceptive. ECa 233 may be alternatively and safely used for treating chronic inflammatory TMD pain, showing an inverted U-shaped dose-response relationship with maximal effect at 100 mg/kg.

Acute enhancing effect of a standardized extract of Centella asiatica (ECa 233) on synaptic plasticity: an investigation via hippocampal long-term potentiation.

CONTEXT: ECa 233 is the standardized extract of Centella asiatica (L.) Urban. (Apiaceae). It contains at least 85% of triterpenoid glycosides and yields neuroprotective and memory-enhancing effects. However, the exact molecules exerting the effects might be triterpenic acid metabolites reproduced through gut metabolism after orally ingesting C. asiatica, not triterpenoid glycosides. OBJECTIVE: This study demonstrates the effect of unmetabolized ECa 233 on hippocampal synaptic plasticity after directly perfusing ECa 233 over acute brain slices. MATERIALS AND METHODS: The brain slices obtained from 7-week-old male Wistar rats were randomly divided into 4 groups. We perfused either artificial cerebrospinal fluid (ACSF), 0.01% DMSO, 10 µg/mL ECa 233, or 100 µg/mL on brain slices, and measured the long-term potentiation (LTP) magnitude to determine the synaptic plasticity of hippocampal circuits in each group. RESULTS: The LTP magnitude of ACSF, DMSO, 10 ug/mL ECa 233, and 100 ug/mL ECa 233 groups increased from 100% to 181.26 ± 38.19%, 148.74 ± 5.40%, 273.71 ± 56.66%, 182.17 ± 18.61%, respectively. ECa 233 at the concentration of 10 µg/mL robustly and significantly enhanced hippocampal LTP magnitude. The data indicates an improvement of the hippocampal synaptic plasticity. DISCUSSION AND CONCLUSIONS: This study emphasizes the effectiveness of triterpenoid glycosides in ECa 233 on synaptic plasticity enhancement. Therefore, this study supported and complimented the known effects of C. asiatica extract on the enhancement of synaptic plasticity, and subsequently, learning and memory, suggesting that ECa 233 could be a promising memory enhancing agent.

Inverted U-shaped response of a standardized extract of Centella asiatica (ECa 233) on memory enhancement.

The herb Centella asiatica has long been considered a memory tonic. A recent review found no strong evidence for improvement of cognitive function, suggesting negative results were due to limitations in dose, standardization and product variation. We used a standardized extract of C. asiatica (ECa 233) to study behavioral, cellular and molecular effects on learning and memory enhancement. ECa 233 (10, 30, and 100 mg/kg) was given orally to normal rats twice a day for 30 days. We used the Morris water maze to test spatial learning and performed acute brain slice recording to measure changes of synaptic plasticity in the hippocampus, a core brain region for memory formation. Plasticity-related protein expressions (NR2A, NR2B, PSD-95, BDNF and TrkB) in hippocampus was also measured. Rats receiving 10 and 30 mg/kg doses showed significantly enhanced memory retention, and hippocampal long-term potentiation; however, only the 30 mg/kg dose showed increased plasticity-related proteins. There was an inverted U-shaped response of ECa 233 on memory enhancement; 30 mg/kg maximally enhanced memory retention with an increase of synaptic plasticity and plasticity-related proteins in hippocampus. Our data clearly support the beneficial effect on memory retention of a standardized extract of Centella asiatica within a specific therapeutic range.

Bacopa monnieri extract enhances learning-dependent hippocampal long-term synaptic potentiation.

Bacopa monnieri has been used in Ayurvedic medicine as a memory enhancer for a long time; however, its direct effect on synaptic plasticity has not been investigated. To the best of our knowledge, this study is the first to report the effect of B. monnieri on long-term synaptic potentiation in acute hippocampal slices. Adult male Wistar rats were orally administered either sterile water or the ethanolic extract of B. monnieri for 60 days. The extracellular recording was performed to measure the field excitatory postsynaptic potential in the acute hippocampal slices of these rats. Our results showed that B. monnieri extract significantly increased long-term potentiation magnitude compared with the control group, whereas there was no change in basal synaptic transmission. The data support the beneficial mnemonic effect of B. monnieri, and suggest that this effect might be because of the increase of learning-associated synaptic machinery, resulting in the long-term potentiation enhancement and strengthening of hippocampal synapses, which plays a critical role in learning and memory formation.