How might acupuncture provide relief from chronic pain and asthma? Can herbal extracts be used to investigate liver fibrosis? Researchers at the Shanghai University of Traditional Chinese Medicine (SHUTCM) are using new research tools to try to understand the mechanisms at work in these applications of traditional Chinese medicine.
A team led by Jianguang Xu, a surgeon and president of SHUTCM, is examining the possibilities for re-training the neural networks of patients with nerve injury and dysfunction using electroacupuncture, a technique that uses the electric stimulation of thin needles inserted at specific points through the skin. In recent years, this modification of the traditional Chinese medicine technique has been studied for its application in the treatment of neuropathic pain, Xu explains.
Xu says that chronic pain sometimes occurs at a site of peripheral nerve injury long after it has healed. While chronic pain is still being studied, one theory, says Xu, is that the original injury may trigger a synchronized activation pattern in the neurons of the brain’s limbic system, which is responsible for memory, and responses to touch and pain.
“We would like to take advantage of neuromodulation, a technique that modulates neuron activity through electrical stimulation to try to retrain the brain and treat chronic pain,” he explains.
Xu’s team is studying brachial plexus avulsion injuries, where the network of nerves that sends signals from the spinal cord to the shoulder, arm and hand are ripped away and/or compressed.
Brachial plexus avulsion injury often occurs in car accidents, and is estimated to affect 7−10% of global population. The recurrent shooting and burning that sometimes follows these injuries, known as neuropathic pain, is one of the most intractable types of chronic pain, says Xu.
In a randomized controlled study of 32 rats with brachial plexus avulsion injury, Xu’s group used electroacupuncture five times a week for 12 weeks. In the electroacupuncture group, researchers saw evidence of increased metabolic connectivity in the right somatosensory cortex, the region of the brain responsible for processing sensory information such as touch, temperature and pain. Metabolic changes also occurred in the emotion- and cognition-related brain regions, Xu adds.
This increase in brain activity described by the team in Frontiers in Neural Circuits in 2020 suggest these areas are changing or have a greater capacity for being ‘rewired’ to break pain patterns, says Xu.
“In conjunction with studying the molecular mechanisms, we are doing clinical work to see if we can retrain the brain’s limbic system by suppressing pain responses using electroacupuncture while a patient does certain exercises or responds to triggers using robot-mediated movement or virtual reality tools,” he adds.
Looking for implications for asthma
Another group at the university is examining acupuncture’s effect on metallothionein-2 (MT-2), a protein linked to the relaxation of airway smooth muscle cells (ASM), which contract during asthma, leading to shortness of breath.
A team led by Yong-Qing Yang, vice president of SHUTCM, is examining the effect of acupuncture on the expression of MT-2.
Acupuncture is often used to treat asthma in China. So, in a study published in the Journal of Biomedical Science in 2009, Yang’s group used serial analysis of gene expression and bioinformatic tools to compare gene expression before and after rat models of asthma were treated with acupuncture. They found 21 biomarkers linked to specific genes and concluded they may be activated by acupuncture, including the gene responsible for MT-2. “This research helped to clarify the mechanisms that may be at work in acupuncture in treating asthma,” says Yang.
In a 2018 follow up, published in Science Translational Medicine, Yang’s team showed that MT-2 binds to transgelin-2 (TG-2), a novel therapeutic target found on the membranes of ASM, and that this interaction induced relaxation of these cells.
Then in a randomized, controlled rat model study published in Biomedicine & Pharmacotherapy in 2020, the team treated asthmatic rat models with acupuncture on alternate days for two weeks. The asthmatic group of rats registered significantly less airway contraction after treatment, and MT-2 mRNA expression in lung tissue increased throughout the study in the rats treated with acupuncture, explains Yang.
While the research is at an early stage, further investigation of the therapeutic potential of TG-2, and agonist molecules that bind to and activate TG-2, may be able to help clinicians improve current asthma treatments, Yang concludes.
Learning about the liver
Ping Liu, a hepatologist at SHUTCM, and his team, are examining the effect on the liver of a decoction of plant-derived components based on a herbal remedy found in traditional Chinese medicine.
The extract is made from Salvia miltiorrhiza, Prunus persica (L.) Batsch, Ophiocordyceps sinensis (Berk.) Sacc., Pinus massoniana Lamb., Schisandra chinensis (Turcz.) Baill. and Gynostemma pentaphyllum (Thunb.) Makino.
It has been tested for its effect on the progression of liver fibrosis, a condition that commonly develops alongside chronic liver disease, which includes chronic hepatitis and fatty liver.
A six-week randomized controlled study of 48 mice published in Scientific Reports in 2019 suggested that the extraction may inhibit key elements in the progression of liver fibrosis to cirrhosis, a late-stage scarring, explains Liu.
The team also was consulted on a multicentre clinical trial in the United States using a formulation of the six components developed by SHUTCM for patients with chronic hepatitis C and hepatic fibrosis. Between 2009 and 2014, hepatologists, Tarek Hassanein, from the University of California, San Diego, and John Moore Vierling, from Baylor College of Science, conducted a phase II double-blind, randomized, controlled clinical trial on 118 patients using the extract. They were encouraged by the results.
Raising standards
Zhengtao Wang, director of Shanghai R&D Center for Standardization of Chinese Medicine at Shanghai University of Traditional Chinese Medicine is chemically profiling the compounds in the extractions. One of Wang’s priorities is to analyze and produce these extraction components with much greater precision.
“While conventional quality control often relies on quantifying a single marker substance, locating these chromatographic fingerprints has shown great advantage in mapping the entire metabolic profile of herbal medicines,” he explains.
His team has adopted an integrated approach using an analysis technique known as ultra-performance liquid chromatography, equipped with diode array detection and electrospray ionization mass spectrometry, to characterize the principal polyphenol constituents in health supplements and potential drugs.
According to Wang, investments to upgrade laboratory equipment to clarify the composition of each plant component is crucial, not just for developing new drugs and supplements, but also for international acceptance via studies on the bioactive function of plant components, as well as quality control.
Wang’s aim is also to ensure stability and standardized quality to provide best protocols on safety and stability of herbal sources. “One major problem is that cultivation locations and time cycles may lead to inconsistencies even when using the same species and technologies,” he says.
“The production yield of extractives from raw herbal material containing bioactive ingredients can sometimesvary widely. We have to getthe technologies in place to achieve a bioactive consistency within a limited variation range,” he says.
Global export
In its efforts to modernize the research of traditional Chinese medicine, SHUTCM has partnered with many international research centres.
Among the first was SHUTCM’s Japanese arm, the Shanghai University of Traditional Chinese Medicine Education College, in Osaka. The college launched in 1990 with governmental support from China and Japan and is one of few recognized educational institutions dedicated to traditional Chinese medicine in Japan. Shigeo Yao, who studied at SHUTCM and worked at the Shanghai General Hospital before completing his doctoral studies at the Graduate School of Medicine at Kobe University, has been the college president since 2018.
“I’m honoured to share this confluence of traditional Chinese medicine and modern technology with my alma mater and to focus on promoting health and well-being and preventative healthcare,” Yao says.
In April 2021, the college opened a wet lab in nearby Kobe, at the Honjo Kobe Research Center for Biomedical Innovation as part of a local government initiative partnering with the Foundation for Biomedical Research and Innovation at Kobe.
SHUTCM is also working beyond Asia, launching its first postgraduate class, a Master of Arts in Traditional Chinese Medicine and Culture at the University of Malta, in November 2015.
“This was the first programme in which we partnered with an international comprehensive university. The aim is to attract working healthcare professionals looking to upskill,” explains Xu. “Thanks to the ‘Belt and Road’ initiative, we have also established Chinese healthcare centres in the Czech Republic, Morocco, Thailand, Mauritius, and Malta.”
SHUTCM was inaugurated in 1956, in 2020 it was ranked 65th in China in terms of annual funding according to the National Natural Science Foundation of China. It houses three key laboratories and two engineering centres run through China’s Ministry of Education. Its network includes nine affiliated hospitals that also provide training for its students.
“Our framework works to better integrate traditional Chinese medicine as a complementary practice in healthcare,” says Xu.
