Gastrodia elata Blume (Tianma): Hope for Brain Aging and Dementia

Abstract

Since aging-related diseases, including dementia, represent major public health threats to our society, physician-scientists must develop innovative, interdisciplinary strategies to open new avenues for development of alternative therapies. One such novel approach may lie in traditional Chinese medicine (TCM). Gastrodia elata Blume (G. elata, tianma) is a TCM frequently used for treatment of cerebrocardiovascular diseases (CCVDs). Recent studies of G. elata-based treatment modalities, which have investigated its pharmacologically relevant activity, potential efficacy, and safety, have employed G. elata in well-characterized, aging-related disease models, with a focus on models of aging-related dementia, such as Alzheimer's disease (AD). Here, I examine results from previous studies of G. elata, as well as related herbal preparations and pure natural products, as prophylaxis and remedies for aging-related CCVDs and dementia. Concluding, data suggest that tianma treatment may be used as a promising complementary therapy for AD.

Figure 1

Schematic overview of tianma-mediated CCV-related activities. (a) With astrocytes serving as sensors and mediators between neural signal transmission and the vascular-dependent energy (glucose) supply, tianma can improve vascular activities and, upon uptake into the cerebrum, neuronal activities and survival and provide neuroprotection against ischemic strikes [33, 41]. (b) Quantitative data showing tianma-enhanced vasorelaxation. Elderly rats were treated with tianma for a period of three months (∼2.5 g/kg/day), after which their thoracic aortas were isolated. Dose-response analysis with increasing level of acetylcholine- (ACh-) induced relaxation in KCl (80 mM) or phenylephrine (PE, 10⁻⁶ M) precontracted isolated endothelium-intact arterial rings [67]. (c) Quantitative representation of tianma-increased vascular contractile force and elasticity. Dose-response comparison of maximum contractile force in response to increasing concentration of PE in endothelium-intact thoracic aortic rings (preincubated with 80 mM K⁺) in tianma-treated elderly rats and controls [67].

Figure 2

The effects of tianma on AD-related signaling and cognitive function during aging. (a) Qualitative data showing the effects of tianma and other herbs on APP processing. Estimation of soluble sAPPα level in cell culture supernatant (measured by enzyme-linked immunosorbent assay (ELISA)) and relative beta-secretase 1 (BACE1) expression (evaluated by Western blot analyses) of neuronal cells treated with tianma. Neurons were grown and treated with certain concentrations of tianma or other herbs for 24 h. Data are qualitatively represented as relative changes compared with controls. Only tianma-treated neurons showed significant increase of sAPPα level and significantly reduced BACE1 expression [44, 46]. (b) Schematic overview of the impact of tianma on APP processing. At the measured concentrations, tianma inhibits BACE1, promotes sAPPα production, suppresses amyloid beta peptide (Aβ) plaque formation, and reduces microtubule-associated protein tau (MAPT) phosphorylation, thereby fostering the nonamyloidogenic pathway [42, 44, 46]. (c) Qualitative data showing the effects of tianma on cognitive function. Tianma enhances memory, learning, and executive function in elderly rats during the Morris water maze, object recognition, and attention set shift tests [32, 41, 43, 46, 49]. (d) Schematic overview of the mechanisms underlying the effects of tianma on dementia. Tianma markedly improves cognitive abilities and protects against aging-related dementia, memory impairment, and neurodegeneration by restoring and rejuvenating cerebrovascular functions in elderly rats [, , , , –44, 46, 49, 72].