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

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.


Introduction
Aging-related dementia, which is mediated by damage to brain cells induced by pathways, such as those underlying Alzheimer's disease (AD), cerebrocardiovascular diseases (CCVDs), and other neurodegenerative diseases (NDs), is causing great inquietude, anxiety, and discomposure in an aging society [1][2][3][4][5][6][7]. e World Health Organization (WHO) has recognized the imperative for globally coordinated research to combat dementia [8]. Much hope has been based on use of stem cell-based therapies; however, such approaches still have to overcome major challenges [9]. us, with dementia posing a health threat to elderly people, social awareness of healthy lifestyle choices that can prevent aging-related neuroinflammation and cognitive dysfunction has been attracting increasing attention. In particular, a healthy diet, exercise, and caloric restriction have been demonstrated to be preventive against new-onset AD and to effectively ameliorate the symptoms of AD [10,11]. Familial (early-onset, younger than 65 years) AD is caused by genetic mutations [12][13][14][15]. However, the majority of AD cases (∼95%) is the sporadic non-inherited form, which is also referred to as late-onset (non-familial, sporadic) AD [14,16]. Sporadic AD is likely caused by normal aging [16,17] and its associated consequences, including oxidative stress and disturbance of protein homeostasis [13,[18][19][20].
Recently, many companies have stopped their AD-related clinical trials and minimized their investments in neurological studies [21]. erefore, we need new approaches to open doors for alternative therapeutic strategies against aging-related NDs and dementia. In the past few years, alternative medicine has come into focus for the potential to provide new therapeutic measures for dementia [22][23][24][25]. Recent comparative proteomics research studies regarding AD-related TCM treatments revealed novel data that suggest that potential mechanisms of action of TCM for the prevention of AD pathogenesis involve improving the ubiquitin proteasome system (UPS, including chaperones and cochaperones (notably, heat shock proteins (HSPs) and FK506 binding proteins (FKBPs))) [20,26]. Particularly, G. elata (tianma) received special attention and will therefore be discussed in more detail as follows [26].
Evidence-Based Complementary and Alternative Medicine atherosclerosis, and stroke, by facilitating vasodilatory effects that strengthen the arterial structure. erefore, identification of all the bioactive ingredients in tianma could help facilitate its application as an efficient therapeutic herbal medicine for treatment of CCVDs by elucidating the mechanisms by which it ameliorates these abnormal cardiovascular responses [33,41,54,67,70,71].

Interference Prevents Protein Misfolding during Aging and in NDs.
e proposed pathomechanism underlying AD involves Aβ plaque formation, NFTs, and deregulation of chaperone proteins. Consequently, in AD brains, an impaired UPS system is thought to account for Aβ aggregation and hyperphosphorylated MAPT-mediated NFT formation, which is potentially furthered by an irregular APP intracellular domain (AICD) signaling pathway [20]. e various protein groups modulated by tianma treatment affect the UPS system, and active tianma ingredients also target molecular chaperones and cochaperones, such as HSPs and FKBP, and modulate the actions of protein phosphate PP2A. Together, these data open new avenues for future investigations into the prophylactic effects of tianma for aging-related dementia and NDs (Figure 2(d)) [20,26].

Conclusion
e human brain, with its high-level cognitive functions, requires a large degree of flexibility and adaptability for appropriate learning and memory and is very vulnerable to cerebrovascular injuries, such as ischemia or stroke, which can cause NDs and dementia. Tianma has been shown in human clinical studies to be effective against VD [40], and various pre-clinical studies have demonstrated at the molecular and cellular levels its potential as an efficacious anti-aging elixir.

Conflicts of Interest
e author declares no conflicts of interest.