Chinese herbal medicine for asthma: an evaluation of traditional and scientific evidence
Creators: name: CLYNE, Ally
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 420803
subject: Traditional Chinese medicine and treatments

description: Asthma is a chronic respiratory condition defined by its associated clinical symptoms. Conventional treatments are effective at controlling the symptoms of asthma; however, these are temporary and there are associated risks and adverse effects with long-term use. Consequently, these risks and adverse effects may increase the appeal of Chinese herbal medicine (CHM) as a complementary therapy for asthma.

The primary aim for this project was to evaluate the traditional and scientific evidence of CHM for asthma. This was approached methodologically using a five-phase method to identify a potentially effective CHM formula and analyse its prospective mechanisms of action as follows: (1) Phase 1 reviewed the existing scientific evidence regarding CHM and asthma and identified a potentially effective formula (Ding Chuan Tang 定喘汤 [DCT]), (2) Phase 2 was a text-mining study that examined the development of DCT formula variations, ingredients and therapeutic indications throughout classical CHM literature, (3) Phase 3 reviewed the existing clinical and experimental evidence for DCT and asthma, (4) Phase 4 identified and compared the physicochemical properties of DCT-compounds with the physicochemical properties of known anti-asthmatic compounds (AACs), and (5) Phase 5 involved the molecular docking investigation of DCT-compounds. Phase 5 included two stages to (i) distinguish potential target proteins and biological mechanisms of action related to asthma, and (ii) investigate the possibility of an optimised DCT formula without the Australian restricted herbal ingredients Ma huang 麻黄 (Ephedrae Herba) and Kuan dong hua 款冬花 (Farfarae Flos).

<strong>Phase 1: Systematic review and meta-analysis of Chinese herbal medicine for asthma</strong>

The systematic review (Chapter 4) resulted in 18 randomised controlled trials (2,080 participants) that compared a CHM with a placebo. Meta-analyses used random effects in RevMan 5.3 and baseline values were assessed for asthma severity. The application of certain CHMs adjunctive to conventional medications improved outcomes in acute and chronic asthma; however, most evidence was based on a single trial. Effect sizes varied according to asthma severity at baseline, with moderate and/or severe baseline asthma improvements more evident. DCT was highlighted in this review, as it was the subject of one of the randomised controlled trials of chronic asthma that showed high methodological quality and no associations with adverse effects. Furthermore, two epidemiological studies, each surveying over 20,000 asthma patients, found DCT to be the highest prescribed CHM formula in Taiwan for asthma in both children and adults.

<strong>Phase 2: Text mining of classic literature for Ding Chuan Tang</strong>

The search of over 1,000 classic texts resulted in 143 formulae containing the name DCT within 96 classical Chinese medical texts (Chapter 5). Within the investigated texts, a total of 94 individual herbs were identified from formulae named DCT that provided the full prescription. Of these 94 herbs, the top nine were the components of the current DCT formula identified for this project: Bai guo 白果 (Ginkgo Semen), Ma huang 麻黄 (Ephedrae Herba), Su zi 苏子 (Perillae Fructus), Gan cao 甘草 (Glycyrrhizae Radix et Rhizoma), Kuan dong hua 款冬花 (Farfarae Flos), Xing ren 杏仁 (Armeniacae Semen), Sang bai pi 桑白皮 (Mori Cortex), Huang qin 黄芩 (Scutellariae Radix) and Ban xia 半夏 (Pinelliae Rhizoma). This outlined DCT formula version first appeared in the classical text She Sheng Zhong Miao Fang 摄生众妙方 circa anno Domini (AD) 1504 and then dominated the pre-modern era. This provided additional evidence for selecting this particular DCT formula version as the CHM for further investigation for asthma.

<strong>Phase 3: Literature review of clinical and experimental studies relevant to Ding Chuan Tang</strong>

Following a systematic database search for DCT, its individual herbal ingredients and compounds, three clinical studies and 35 experimental studies were included (Chapter 6). Outcome measures for the clinical studies evaluated primary lung function measures, while outcomes for the experimental studies included any measure of asthma immuno-pathogenesis. The results of both the clinical and experimental studies exhibited potential for DCT to mediate mechanisms that lead to airway inflammation and remodelling. Furthermore, these results suggested potential for DCT for the management of asthma.

<strong>Phase 4: Comparison of physicochemical properties of Ding Chuan Tang compounds with known anti-asthmatic compounds</strong>

A total of 644 DCT-compounds were identified (Chapter 7). Of these, 396 DCT-compounds with known structures from nine herbs were included for analysis: Bai guo 白果 (n=40), Ma huang 麻黄 (n=40), Su zi 苏子 (n=30), Gan cao 甘草 (n=100), Kuan dong hua 款冬花 (n=15), Xing ren 杏仁 (n=17), Sang bai pi 桑白皮 (n=43), Huang qin 黄芩 (n=33) and Ban xia 半夏 (n=78). Forty–eight AACs known to have indications for the treatment of asthma were included for comparison of four physicochemical properties (molecular weight, polar surface area, atomic lipophilicity and solubility) and matching degrees (quantitative estimate of drug-likeness). Seventy-seven DCT-compounds satisfied drug-like criteria based on their physicochemical properties and high matching degrees in comparison with the 48 known AACs.

<strong>Phase 5: Molecular docking of Ding Chuan Tang compounds and asthma-related target proteins</strong>

The molecular docking investigation included 243 DCT-compounds that docked with five protein targets associated with asthma biological pathways including Estrogen receptor alpha (ESR1), Kinase insert domain receptor (KDR), Leukotriene A4 hydrolase (LTA4H), cAMP-specific 3’,5’-cyclic phosphodiesterase 4D (PDE4D), and Peroxisome proliferator-activated receptor gamma (PPARG) (Chapter 8). Pharmacological network connections were established and results for 155 DCTcompounds demonstrated direct involvement with asthma inflammatory and metabolic signalling pathways. Additionally, these results, albeit computational, highlighted the multi-target and synergistic therapeutic effects defined by the varying indications for DCT throughout CHM history.

In conclusion, the investigation of traditional and modern literature within this project has indicated DCT to be a clinically promising CHM formula for the management of asthma. The computational analyses further investigated the mechanisms of action of DCT for asthma which indicated DCT’s multitarget effects for asthma. Future studies may focus on the validation of these computational results including the optimisation/simplification of DCT through laboratory experiments and clinical trials.