Comments on Chinese Medicine Research Papers Published in The Lancet

 Tiejun Tang    

A recent research paper published in the internationally renowned medical journal The Lancet titled "Traditional Chinese Medicine FYTF-919 (Zhongfeng Xingnao Oral Prescription) for the Treatment of Acute Cerebral Hemorrhage: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial" ^[1] concluded that the efficacy of the traditional Chinese medicine (TCM) prescription, Zhongfeng Xingnao Oral Prescription, was no different from that of a placebo, and it could not improve the functional prognosis, survival rate, or quality of life of patients with cerebral hemorrhage. This conclusion could easily mislead readers into thinking that traditional Chinese medicine is ineffective in treating cerebral hemorrhage, causing a negative impact on the reputation of TCM and provoking strong responses from the TCM community both domestically and internationally.

But is it really true that traditional Chinese medicine is ineffective in treating cerebral hemorrhage? No! The conclusions of this study only show that the specific prescription used in the trial is ineffective, and they cannot be generalized to all traditional Chinese medicines. The main issue with the negative research results lies in the selection of the prescription.

Zhongfeng Xingnao Oral Prescription contains four ingredients: Hongshen, Sanqi, Chuanxiong, and Dahuang. My opinion is using Chuanxiong in the treatment of acute cerebral hemorrhage is fundamentally incorrect.

The Chinese Pharmacopoeia records that Chuanxiong is pungent, warm, and acts on the liver, gallbladder, and pericardium meridians. It is known for promoting blood circulation, dispelling wind, and relieving pain. It is typically used for irregular menstruation, dysmenorrhea, abdominal pain due to lumps, stabbing chest and rib pain, swelling and pain from injuries, and headaches. In clinical practice, Chuanxiong is recognized for its ability to promote blood circulation and remove blood stasis, making it an important medicine for treating headaches. Modern pharmacological studies have confirmed that the main active ingredient of Chuanxiong is ligustrazine. The pharmacological effects of Chuanxiong and ligustrazine have been hotly researched, with over 1,000 articles available on PubMed when searching for "Chuanxiong" or "ligustrazine" (1022 and 1608 papers, respectively). In 2024 lone, there were 96 and 115 studies published on the topic.

Recent studies on Chuanxiong’s effect on coagulation and blood rheology reveal some concerning findings:

1. One study using network pharmacology found that Chuanxiong can inhibit TF (tissue factor) procoagulant activity and reduce TF mRNA and protein expression in EA.hy926 cells in a dose-dependent manner via the PI3K/Akt/NF-κB signaling pathway ^[2].
2. Another study using affinity ultrafiltration mass spectrometry (AUF-MS) identified 21 active components from Chuanxiong, with ferulic acid, chlorogenic acid, and isochlorogenic acid A being potential antithrombin agents. The conclusion was that Chuanxiong is a Chinese herbal medicine with good anticoagulant effects ^[3].
3. A third study using a microfluidic chip model of normal and stenotic arteries showed that ligustrazine inhibits platelet aggregation and activation by reducing the binding of von Willebrand factor (vWF) to the GPIb/IX/V complex, partly inhibiting platelet aggregation through the P2Y12-ADP receptor pathway ^[4].

Ligustrazine has effects such as inhibiting platelet aggregation, dilating blood vessels, reducing blood viscosity, and anticoagulation. It is mainly used in the treatment of ischemic stroke and can be employed for rehabilitation in hemorrhagic stroke. However, it is obviously unsuitable for use in the acute stage of cerebral hemorrhage, as its anticoagulant properties could worsen bleeding.

In contrast, Western medicine uses hemostatic drugs such as aprotinin, 6-aminocaproic acid, and tranexamic acid in treating acute cerebral hemorrhage to correct coagulation dysfunction and prevent the expansion of the bleeding area. Although the clinical effect of hemostatic drugs is not ideal, they remain one of the routine treatments for acute cerebral hemorrhage. The effect of ligustrazine on coagulation is completely opposite to that of hemostatic agents.

Traditional Chinese medicine (TCM) holds that "blood that leaves the vessel is stagnant," and there are indeed reports of using blood-activating and blood-stasis-removing methods to treat cerebral hemorrhage. However, this is generally applied in the recovery period, not in the acute phase. TCM often uses Sanqi (Panax notoginseng), which has both blood-activating and hemostatic effects, in such treatments. The two ingredients, Chuanxiong and Dahuang, in this particular prescription both promote blood circulation, which does not align with the TCM principles of syndrome differentiation and treatment. This discrepancy likely led to the negative research results in the study.

For treating acute cerebral hemorrhage, TCM must follow the principle of syndrome differentiation. For example:

• Angong Niuhuang Wan clears heat, resolves phlegm, and opens the orifices, suitable for phlegm-heat blocking type stroke.
• Shenfu Tang is used for yang qi exhaustion syndrome.
• Shengmai San is used for qi and yin deficiency syndrome.

There is no single prescription that can effectively treat all types of strokes.

Furthermore, scientific research on TCM must respect the inherent principles of TCM. It cannot simply replicate the Western medical research model, as this approach would lead to biased conclusions.

References:

1. Jianwen Guo. Traditional Chinese Medicine FYTF-919 (Zhongfeng Xingnao Oral Prescription) for the Treatment of Acute Intracerebral Hemorrhage: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial. The Lancet, 2024 Nov; Volume 404, Issue 10468, Pages 2187-2196.
2. Shasha He. "Exploring the Mechanism of Chuanxiong Rhizoma Against Thrombosis Based on Network Pharmacology, Molecular Docking and Experimental Verification." Molecules, 2023 Sep 19; 28(18): 6702.
3. Chencun Huang. "Screening of Anti-Thrombin Active Components from Ligusticum Chuanxiong by Affinity-Ultrafiltration Coupled with HPLC-Q-Orbitrap-MS." Phytochemical Analysis, 2023 Jun; 34(4): 443-452.
4. Tiancong Zhang. "Application of Microfluidic Chip Technology to Study the Inhibitory Effect of Tetramethylpyrazine on Platelet Aggregation, Activation, and Phosphatidylserine Exposure Mediated by Pathological High Shear Rate." Blood Coagul Fibrinolysis, 2023 Jan 1; 34(1): 47-60.

The best reward for my 40 years clinical practice

Tiejun Tang

This year marks the 40th anniversary of my graduation from the University of Traditional Chinese Medicine, which marked the beginning of my career as a TCM doctor and university teacher. 

An International Chinese media and an authoritative academic institution selected 22 The Overseas Grand Master of Traditional Chinese Medicine and 155 Famous Practitioner of Traditional Chinese Medicine in the world. I am very honored to be selected as one of the 22 Overseas Grand Master of Traditional Chinese Medicine. This is the best reward for my 40 years career.

The certificate of the Overseas Grand Master of Traditional Chinese Medicine was received. I would like to thank the selection committee for their excellent work. Unfortunately, due to the time arrangement, I was unable to attend the awards ceremony in Vancouver today. I wish the conference had successfully accomplished.

At this moment, I would like to say a few words to express my feelings from the bottom of my heart:

First of all, I would like to thank my teachers in the past 45 years since I had entered the world of Traditional Chinese Medicine, including all of my teachers in my undergraduate, MSc, PhD and post-doctoral research stages. I would like to thank every alma mater where I studied and worked together for the past years.

Also, I would like to thank the countless of patients that I had treated in China and the UK in the past 40 years. Your suffering is my motivation to keep making progress. Practitioners' knowledge comes from learning, but most of their clinical experience comes from patients’ feedback

I would like to thank my students who based in China, UK and Europe in the past 40 years. Teaching and learning always enhances each other. Being a good teacher and leading my students on the right path is an additional motivating force to continue my journey.

I would like to thank my classmates, colleagues, and friends at all stages who have supported and helped me over the years. 

At last, I would like to thank my family and relatives who have given me a great support all along.

I’m so grateful to have you all in my life.

Precancerous lesions and complementary medicine approach

 TiejunTang 

In recent years, we have often heard bad news about someone who suffers from any type of cancer. According to the statistics of the Cancer Research UK, there are around 375,000 new cancer cases in the UK every year (2016-2018), and around 167,000 cancer deaths in the UK every year (2017-2019). World Cancer Research Fund reported there were 18.1 million cases of cancer diagnosed in 2020 globally.

The prognosis of different cancers are various. Some are completely curable due to the development of medical science; unfortunately some are not. Although they are incurable, we can prevent it. Cancers take time to develop; they often develop from some chronic diseases. These diseases are often called precancerous lesions. If you are being treated appropriately, the condition could be under control.

Below are some examples of common precancerous lesions and the effectiveness of Chinese herbal medicine in these conditions.

1. Atypical Breast Hyperplasia → Breast Cancer

Breast cancer is one of the most common cancers, and it often develops from inconspicuous precancerous lesions, such as breast atypical hyperplasia, intraductal papilloma and cystic breast hyperplasia, which are all considered to be precancerous lesions.

From the perspective of traditional Chinese medicine (TCM) , breast hyperplasia is a condition that causes by stagnation of liver qi, which leads to the blockage of qi in the body, resulting in breast pain. TCM herbs that soothe the liver and relieve stagnation can be given to intervene. Commonly used herbs are Xiangfu, Qingpi and Chenpi for soothing the liver and regulating qi. Chishaoyao can be added to activate blood circulation and remove blood stasis, Gualou can be added to resolve phlegm and dissipate stagnation, and Banzhilian & Baihuasheshecao can be added for anti-cancer, as well as reducing the risks of getting breast cancer.

A molecular level experimental study showed: The Chinese herbs Huangqi, Renshen, Fuling and Chaihu, as well as some other herbal formulas can regulate the genetic related and protein expression via pathways such as PI3K/AKT/mTOR, MAPK and Wnt/β-catenin, which inhibits the growth, proliferation, migration, invasion and metastasis of triple-negative breast cancer cell^.[1]

2. HPV Infection → Cervical Cancer

HPV (human papillomavirus), is divided into high-risk, intermediate-risk and low-risk types according to the risk of causing cervical cancer. Among them, 13 types of viruses are considered in the high-risk category. In the worldwide, there are 90% of cervical cancers are caused by HPV.  In the Western medicine, there isn’t any specific medication for treating HPV, however, It can only be relied on our immunity to cure the disease. In some cases, most of the infections can be healed by themselves within 2 years, however, some patients are potentially suffering from the cervical cancer in the end.

Traditional Chinese Medicine (TCM) believes that this disease is mostly caused by damp-heat, spleen-deficiency, endogenous dampness, as well as toxins which are one of the primary pathologies. Treatment is usually based on strengthening the spleen and removing dampness, clearing away the heat and detoxifying.  The modified formula of the Traditional Chinese medicine, the Simiao Decoction is used in the treatment of HPV, showing the satisfactory efficacy.

The Research shows that the mechanism of Chinese herbal medicine may perform on the regulation of cell apoptosis, viral gene transcription and translation, cell signal transduction pathways and the immune function.^[2]

3. Colon Polyps → Colon Cancer

Colon cancer is relatively one of the common cancers in the UK, and a large proportion of colon cancers develop from the polyps. Adenomatous polyps have a higher probability of becoming cancerous.  As the size of adenomatous polyps grows, their growth rate is also increased with the total canceration rate ranging from 10% to 20%, therefore, the Western medicine uses endoscopic electrocoagulation resection for the treatment of intestinal polyps, and the recurrence rate is very high.

TCM believes that the causes of colon polyps is due to damp heat, phlegm, and blood stasis that accumulate in the large intestine. The principles of treating this disease are to strengthening the spleen and replenishing the qi, clear away damp heat, and resolve phlegm and blood stasis. In my master degree research in the early 1990s, I applied Jianpi Yikan Pills to treat the intestinal polyps and a satisfactory result was achieved. This patent remedy can be significantly reduced the postoperative recurrence of intestinal polyps^.[3]

4. Chronic Atrophic Gastritis → Stomach Cancer

For chronic stomachache patient, a gastroscopy is necessary. If the biopsy result of the gastroscopy is chronic atrophic gastritis, We must pay more attention to it, especially if it is accompanied by atypical hyperplasia and intestinal metaplasia, a high risk of stomach cancer is associated.  It is generally believed that the canceration rate is: 3% to 5% in 5 to 10 years, and 10% in more than 10 years. 

TCM believes that the etiology and pathology of atrophic gastritis may include liver and stomach qi stagnation, spleen and stomach deficiency, stomach-yin deficiency or stomach blood stasis. The herb selection should depend on the symptoms of individual cases: Chaihu, Foshou to soothe the liver and relieve the liver qi stagnation ; Dangshen and Baizhu to strengthen the spleen and stomach Qi; Maimendong, Shashen and Shihu to nourish stomach yin;  Chishaoyao and Danshen to remove blood stasis.

Research shows that the mechanism of TCM in treating chronic gastritis include the eradication of Helicobacter pylori, the anti-inflammatory effects, the immune regulation, and the regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels^[4].

5. Pulmonary Nodules → Lung Cancer

Chronic cough has increased since the pandemic of COVID-19.  Many people were diagnosed with pulmonary nodules after Covid.  This disease may lead to lung cancer, among which atypical adenomatous hyperplasia which is a type of precancerous lesion.  The bigger the nodule, the higher risk of malignant transformation. People with lung cancer family history are more likely to develop cancer in their lung nodules.

Nevertheless, there is no evidence that pulmonary nodules can be treated by any western medicines, and the surgical operation is necessary for the larger nodules, although the new nodules may reoccur after the surgery.

TCM believes that the main pathogenesis of pulmonary nodules is: deficiency, phlegm, blood stasis, and poison. The treatment principles are to nourish the spleen and lungs, resolve phlegm and detoxify, and dissipate blood stasis and dredge the collaterals.

Usually, Huangqi and Dangshen are used to replenish the qi of the spleen and lungs; Banxia, Qianhu, Zhebeimu and Gualou are used to resolve phlegm and relieve cough, Banzhilian and Yuxingcao are used to clear away heat and detoxify; Sanqi and Danshen are used to activate blood circulation and remove blood stasis.

The Molecular biology and pharmacology research shows that the traditional formula, QianJin WeiJing decoction (QJWJ) can inhibit the growth of lung cancer A549 cell line in a time-dependent manner, which may inhibit the growth of lung cancer cells by inhibiting EGFR and STAT3 signaling pathways, and arresting the cell cycle in G0/G1 phase. The other research showed QJWJ can induce apoptosis in lung cancer cells and enhancing immunity in lung cancer patients. ^[5]

6. Cirrhosis → Liver Cancer

Viral hepatitis is a very common disease in China. In about 10-30% of chronic hepatitis B patients develop cirrhosis within 5-10 years, besides, 5-10% of cirrhosis patients develop liver cancer within 5-10 years as well.  Cirrhosis is considered as a precursor to liver cancer. Although viral hepatitis is relatively rare in the UK, alcoholic cirrhosis becomes the risk factor of liver cancer.

TCM has accumulated immeasurable clinical experiences in treating chronic liver diseases over thousands of years. For those with hypochondriac pain and swelling pain, Chaihu, Qingpi, and Chunlianzi can be used to promote qi and relieve pain; for jaundice conditions, Yinchen, Dahuang and Zhizi can be selected to clear away damp heat and relieve jaundice; for ascites conditions, Fuling, Zexie, Dafupi can be added to diuretic and expel dampness; for patients with hepatosplenomegaly, Danshen, Sanleng, Ezhu can be given to promote the blood circulation and remove blood stasis, or Guiban and Biejia can be used to soften the hardness; for those with cancer tendencies, Banzhilian and Baihuasheshecao can be added to prevent the occurrence of tumors.

There was a cohort study that counted 127,237 liver cancer patients, of which 30,992 (24.36%) were treated with Chinese herbal medicine. Compared with patients who did not use Chinese herbal medicine, The TCM group showed a significantly lower risk of death. Modified Xiaoyao San and Chaihu Shugan San were the most effective formulas for improving survival.  ^[6]

Most importantly, getting early diagnosis and treatment are the most crucial part, as it has a great impact on the patient’s prognosis.

Paying enough attention to the treatment of precancerous lesions can slow down or stop the canceration of cells and avoid the occurrence of cancer. Clinical practice has proven that traditional Chinese medicine can have advantages to the treatments listed above dedicated to precancerous lesions, and its mechanism of action has been confirmed by a variety of scientific studies.

Be aware of the precancerous lesions and eliminate potential risks of cancer is the right choice of your health.

Reference:

1. Zimei Yang. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J Ethnopharmacol. 2021 Jan 10:264:113249.

2. Jing Lin. Traditional Chinese medicine for human papillomavirus (HPV) infections: A systematic reviewBiosci Trends. 2017 Jul 24;11(3):267-273.

3. Tiejun Tang. The effect of JPYK pill on T cell subpopulation and immunological function of spleen asthenia mice. Pharmacology and Clinics of Chinese Materia Medica. 1992; 8 (Sep.): 181.

4. Liangjun Yang. Progress in traditional Chinese medicine against chronic gastritis: From chronic non-atrophic gastritis to gastric precancerous lesions Heliyon.2023 May 27;9(6):e16764

5. Peiyu Liu. A Chinese classical prescription QianjinweijingDecoction in treatment of lung cancer: An overview. Biomed Pharmacother. 2022 Dec:156:113913

6. Yueh-Hsiang Liao. Adjunctive traditional Chinese medicine therapy improves survival of liver cancer patients. Liver Int. 2015 Dec;35(12):2595-602.

Comments on the red yeast incident in Japan

 Tiejun Tang

Recently, there are many people in Japan have been hospitalized or even died due to kidney disease after taking health products containing red yeast rice which produced by Kobayashi Pharmaceutical Company. As of the evening of the 28^th March 2024, there were 5 people died and 114 were hospitalized because of the products. It aroused a great attention in Japan and also, many people were alarmed by the incidents, as well as the safety of how to consume the health care products appropriately.

Red yeast rice have been consuming as food and medicine in China for nearly 700 years. In one of the classic books regarding the food and nutrition - "Yin Shan Zheng Yao", which was published in 1330, was stated that this product had the effects of strengthening the spleen, replenishing qi, and warming the stomach at the time.  Li Shizhen, a famous Chinese herbalist in the Ming Dynasty, the author of "Compendium of Materia Medica" also mentioned that red yeast rice had the same beneficial effects.

In 1979, a Japanese scholar Akira Endo isolated Monacolin K from red yeast rice. In 1985, an American scientists Goldstein and Brown further proposed the mechanism of action of Monacolin K in inhibiting cholesterol synthesis, and thus obtained Nobel Prize, therefore, Monacolin K is regards as the first inventor of statins.

Lowering cholesterol is one of the advantages of taking Statin, but for long-term, it shows some side effects.^[1] According to the results of many pharmacological studies and randomized controlled clinical trials showed that red yeast rice has lipid-lowering effects similar to those of statins^[2-4],  as a natural statin drug, it is relatively safer and is widely used in the treatment of hyperlipidemia in China and Japan.

In traditional Chinese medicine, red yeast often combine with Shanzha (Hawthorn) and  Zexie (Alismatis Rhizoma) and other ingredients that have the similar effect of lowering blood lipids compared with Statin. They are not only lower cholesterol but also reduce triglycerides and balance lipoprotein metabolism.  A research report showed that Chinese herbal medicine, Shanzha have better function in reducing low-density lipoprotein cholesterol (LDL-C) compare to Simvastatin. ^[5] A molecular biology and network pharmacology study showed that Zexie decoction can decrease total cholesterol (TC), Triglycerides (TG) and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo.^[6]

Why was these incidents happened in Japan?  As Red Yeast Rice has always been considered as a safe and healthy food product.  The current investigation believes that it was due to an error in the process of fermentation during the production, the harmpful substances were in the same batch of the production which caused the people got poisoned accidentially.  The specific investigation results are yet to be determined. The further announcements are to be expecting until further investigations.

Such incident was traumatised, and people would become panicked and worried, however, this incident reminds all pharmaceutical companies that GMP standards and the quality control should be strictly followed.  Moreover, the advantages of using Red Yeast Rice for the treatment of hyperlipidemia as a natural medicine is still valuable.

Reference: 

1.      Natalie C Ward.  Statin Toxicity Circ Res. 2019 Jan 18;124(2):328-350.

2.      Cicero AFG  Red Yeast Rice for Hypercholesterolemia. Methodist Debakey Cardiovasc J. 2019 Jul-Sep;15(3):192-199.

3.      Takuya Minamizuka . Low dose red yeast rice with monacolin K lowers LDL cholesterol and blood pressure in Japanese with mild dyslipidemia: A multicenter, randomized trial. Asia Pac J Clin Nutr. 2021 Sep;30(3):424-435.

4.      Peng D, Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults..Am J Nurs. 2017 Aug;117(8):46-54.

5.      Hong Xu. A study of the comparative effects of hawthorn fruit compound and simvastatin on lowering blood lipid levels. Am J Chin Med . 2009;37(5):903-8.

6.      Zhishen Xie. Zexie Tang targeting FKBP38/mTOR/SREBPs pathway improves hyperlipidemia J Ethnopharmacol. 2022 May 23:290:115101

Traditional Chinese Medicine Offers New Option for IBS Patients

Tiejun Tang

Today, April 19th, is the World IBS Day. Irritable bowel syndrome (IBS) is a very common gastrointestinal disorder that causes chronic abdominal pain, bloating, diarrhea, and constipation. According to a pooled prevalence analysis of 53 studies that used Rome III criteria from 38 countries and involved 395,385 participants, the prevalence of IBS was 9.2%, with a higher prevalence in women than in men (12.0% vs. 8.6%) ^[1].

In 2017, I wrote an article titled "How to Treat IBS with Chinese Herbal Medicine and Acupuncture?" (click to read the full text). Since then, more research progress has been made on this topic. This paper is an update discussing of the the recent advancements in the treatment of IBS with traditional Chinese medicine.

Although Western medicine has made progress in treating IBS for the past years, there are still some challenges. The National Institute for Health and Care Excellence (NICE) recommends dietary changes, symptomatic treatment, tricyclic antidepressants (TCAs), and psychotherapy for IBS treatment. However, TCAs are associated with reported side effects of up to 15 symptoms, including severe symptoms such as headache, epilepsy, sexual dysfunction, and weight gain. As a result, many IBS patients may have to deal with persistent symptoms or suffer from the side effects of TCAs. ^[2]

According to the basic theory of traditional Chinese medicine, IBS is mainly caused by the imbalance of liver and spleen. Liver qi stagnation and spleen deficiency are the primary pathologies of IBS. This dissonance can lead to digestive dysfunction, which leads to the symptoms of IBS ^[3]. TCM offers a holistic approach to treating IBS by addressing underlying imbalances in the body. Common Chinese treatments for IBS include herbs, acupuncture, and moxibustion can ease the conditions.

Tongxie Yaofang, a traditional formula that originated in the Ming Dynasty of China, is a common formula for treating IBS. A research report showed it can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to the inhibition of the inflammatory cascade and the NF-κB and Notch signaling pathways^[4]

Wenshen Jianpi Wan is a patent herbal pill which is based on the traditional formula Si Shen Wan. A laboratory research study showed it can reduce visceral hypersensitivity in IBS-D model rats, possibly by down-regulating TNF-α, p-MEK1/2, p-ERK1 in colon tissue and p-ERK2 expression, it also down-regulated the expressions of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus^[5].

Acupuncture is also widely used in the treatment of IBS. A multicenter randomized controlled trial study conducted in 7 hospitals in China showed that acupuncture was more effective than western medicine in treating IBS, and the treatment effect could last up to 12 weeks^[6].

A literature study has analyzed the relevant pathophysiological mechanisms and curative effects of acupuncture in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). It was found that acupuncture can regulate brain-gut peptides in IBS-D patients, change brain connections and activities, promote neuroendocrine function and mental state, and reduce inflammation and intestinal allergies^[7].

In conclusion, clinical and experimental research reports showed that both Chinese herbal medicine and acupuncture can improve IBS symptoms through different mechanisms, and the combination of herbs and acupuncture may bring better results. TCM therapy can completely avoid the side effects caused by western medicine and bring significant benefits to IBS patients.

Reference:

1.  Oka P. Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020; 5(10):908-917
2. Pierre M Bet . Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol. 2013; 23(11):1443-51
3.  Cheng-Jiao Yao,. Traditional Chinese medicine for irritable bowel syndrome. Medicine (Baltimore). 2020; 99(48): e23394.
4. Qiuke Hou. Tong-Xie-Yao-Fang improves intestinal permeability in diarrhoea-predominant irritable bowel syndrome rats by inhibiting the NF-κB and notch signalling pathways. BMC Complement Altern Med. 2019; 19: 337
5. Tianyuan Jiang.  Wenshen-Jianpi prescription, a Chinese herbal medicine, improves visceral hypersensitivity in a rat model of IBS-D by regulating the MEK/ERK signal pathway. Front Pharmacol. 2022; 13: 955421
6.  Lixia Pei. Effect of Acupuncture in Patients With Irritable Bowel Syndrome: A Randomized Controlled Trial. Mayo Clin Proc. 2020; 95(8):1671-1683.
7. Gezhi Zhang. Effects and Mechanisms of Acupuncture on Diarrhea-Predominant Irritable Bowel Syndrome: A Systematic Review. Front Neurosci. 2022;16:918701.

Discuss Parkinson’s Disease in World Parkinson’s Day

 Tiejun Tang  

Today is the World Parkinson's Day. 11^th April is the birthday of Dr. James Parkinson. He is the first physician to recognize Parkinson’s as a medical condition. He was born and practiced in London as a surgeon. In the UK this week is the Parkinson’s disease awareness week. It is observed annually in the UK to raise awareness about the disease and support those affected by it. Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement, causing tremors, stiffness, and difficulty with balance and coordination.   

Over the past generation, the number of individuals with PD globally has more than doubled to over 6 million. In all the neurological disorders included in Global Burden of Disease (GBD) 2015, PD was the fastest growing^[1,2].

Modern medicine offers several treatments for PD, including medication, surgery, and deep brain stimulation. The currently available treatment methods are all symptomatic ones and caused some side effects. No treatment has been proven to slow the progression of PD^[3].

Traditional Chinese medicine believes that PD is mainly caused by deficiency of liver and kidney yin in the early stage; in the middle stage, it is mainly caused by wind phlegm and blood stasis; in the later stage, deficiency of both yin and yang and deficiency of both qi and blood are the main pathology change. In terms of treatment, Chinese medicine applied nourishing yin, detoxifying. Nourishing the qi & blood, and tonified yin & yang^[4].

Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit^[5]. A meta-analysis of 2314 patients showed: Compared with dopamine replacement therapy alone, the addition of acupuncture was significantly beneficial in improving the Unified Parkinson’s Disease Rating Scale score (UPDRS) in PD patients^[6]. The other research showed electroacupuncture on the points of GB34 and LV3 can improve the level of dopamine in the brain of PD animal models ^[7].

Chinese herbs and herbal extracts show potential clinical benefit in slowing the progression of PD in humans. Such as ginseng and ginsenosides, ginkgo biloba and EGb 761, Polygonum multiflorum, and triptolide in Tripterygium wilfordii can alleviate the symptoms caused by the degeneration of dopamine neurons. Herbs or herbal extracts can promote neuronal survival and neurite out rowth, promote functional recovery after brain injury, regulate cell survival genes and signals, anti-apoptotic activity, and improve cerebral blood circulation^[8].

Liuwei Dihuang Wan is a very popular herbal remedy. An network pharmacology research found that: Since they contain several active components, target multiple ligands, and activate various pathways. The hub components possibly include quercetin, stigmasterol, kaempferol, and beta-sitosterol and act through pairing with hub targets, such as AKT1, VEGFA, and IL6, to regulate neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic process, membrane raft, MAPK signaling pathway, and cellular senescence for the treatment of PD^[9].

To further improve the treatment of PD, it is important to integrate the strengths of both Western medicine and TCM. While Western medicine is effective in managing acute symptoms of PD, TCM has shown potential in slowing the progression of the disease and improving the overall quality of life of patients. Therefore, a combination of Western medicine and TCM may provide a more holistic and personalized approach to treating PD, tailored to the individual needs of each patient.

Overall, on this World Parkinson's Day, it is important to raise awareness about PD and support those affected by it. By integrating the strengths of Western medicine and TCM, we may be able to provide better care and improve the quality of life for PD patients.

Reference:

1.  Jacob Stovner. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology. 2018; 17 (11):954-976.
2.  Dorsey ER. The Parkinson pandemic—a call to action. JAMA Neurol. 2018;75(1):9-10.
3. Salawu F. Current management of Parkinson's disease. Ann Afr Med. 2010; 9(2):55-61.
4.  Yuqing Hu. Traditional Chinese medicine syndrome differentiation and treatment by stages of Parkinson’s disease: study protocol for a multicentre, randomized, double-blind, placebo-controlled clinical trial. BMC Chinese Medicine 2022; volume17, Article number: 68.
5. Yadan Zhao. Acupuncture for Parkinson's Disease: Efficacy Evaluation and Mechanisms in the Dopaminergic Neural Circuit. Neural Plast 2021. 15;2021:9926445.
6. Guoxin Zhang. Effectiveness of Traditional Chinese Medicine as an Adjunct Therapy for Parkinson’s Disease: A Systematic Review and Meta-Analysis. PLOS. ONE. March 10, 2015.
7.  Jaung-Geng Lin. Electroacupuncture Promotes Recovery of Motor Function and Reduces Dopaminergic Neuron Degeneration in Rodent Models of Parkinson’s Disease. Int J Mol Sci. 2017; 18(9): 1846.
8. Liang-Wei Chen. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson's disease. CNS Neurol Disord Drug Targets 2007;6(4):273-81.
9.  Dongtao Lin. Study on the Mechanism of Liuwei Dihuang Pills in Treating Parkinson's Disease Based on Network Pharmacology. Biomed Res Int. .2021 . 28;2021:4490081.

How to treat fatty liver?

 Tiejun Tang       

Fatty liver also known as hepatic steatosis, is a growing health concern worldwide. It is estimated that 25% of the global population has fatty liver disease, with prevalence rates as high as 60% in some countries ^[1].

Many people ignore the dangers of fatty liver and leave it untreated, in fact excess fat in the liver can lead to liver damage and negatively affect your health.

The main hazards of fatty liver are as follows:

1) Inflammation: As the liver becomes fatty, it becomes inflamed, which can lead to liver damage and scarring.

2) Liver dysfunction: When the liver becomes inflamed and damaged, it impairs its ability to function properly. This can cause problems with the liver's ability to detoxify blood, produce important proteins, and regulate hormones.

3) Increased risk of type 2 diabetes: Fatty liver disease is associated with insulin resistance, which increases the risk of type 2 diabetes.

4) Cardiovascular disease: Fatty liver disease is also associated with an increased risk of cardiovascular disease, including heart attack and stroke.

5) Liver cancer: In severe cases, fatty liver can develop into liver cancer.

There is no specific medication or treatment specifically approved for fatty liver in Western medicine. Treatment is typically focused on managing any underlying conditions and making lifestyle changes to improve liver health

In Traditional Chinese Medicine (TCM) the liver is regarded as one of the most important organs in the body, responsible for storing blood and regulating the flow of Qi (vital energy) throughout the body. The liver is also associated with the emotion of anger. According to TCM theory, liver Qi stagnation and blood stasis are the main pathological mechanisms of fatty liver disease. This stagnation and stasis can result from various factors, such as overeating, alcohol consumption, and emotional stress, leading to a buildup of fat in the liver ^[2].

In the clinical TCM has been used to treat fatty liver disease for centuries, and clinical studies have shown promising results. For example, a randomized controlled trial involving 80 patients with non-alcoholic fatty liver disease (NAFLD) found that a combination of acupuncture and Chinese herbal medicine resulted in significant improvements in liver function and a reduction in liver fat content compared to the control group ^[3]. Another study involving 60 patients with NAFLD found that treatment with a TCM formula for 12 weeks led to significant reductions in liver fat content and improved liver function ^[4].

The mechanisms of Chinese herbal medicine were investigated through modern pharmacology research. Laboratory research has shown that certain TCM formulas and extracts can reduce fat accumulation in liver cells and improve liver function. For example, a study found that a TCM formula containing rhubarb, baicalin, and choline bitartrate was able to reduce liver fat content and improve liver function in rats with NAFLD ^[5]. Another study found that curcumin, a compound found in turmeric and commonly used in TCM, was able to reduce liver fat accumulation and improve liver function in mice with NAFLD ^[6].

Molecular mechanism research has shown that TCM and its extracts can affect various signaling pathways involved in the development and progression of fatty liver disease. For example, one study found that berberine, a compound found in various TCM herbs, was able to improve liver function and reduce liver fat accumulation by regulating the AMPK/mTOR signaling pathway ^[7].

Overall, the use of TCM for the treatment of fatty liver disease has shown promising results in both clinical practice and scientific research. Further studies are needed to fully understand the mechanisms by which TCM treats fatty liver disease and to optimize its clinical use.

References:

1.   Younossi, Z. M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64(1), 73-84.

2.    Xiong, J. Traditional Chinese medicine for the treatment of nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Journal of Traditional Chinese Medicine. 2019; 39(5), 677-689.

3.    Wu, J., Clinical observation of acupuncture combined with Chinese medicine for the treatment of non-alcoholic fatty liver disease. Chinese Journal of Integrative Medicine, 2016; 22(5), 341-346.

4.   Li, Q. Clinical observation of traditional Chinese medicine formula for the treatment of nonalcoholic fatty liver disease: A prospective, multicenter, observational study. Medicine, 2019; 98(23), e15906.

5.   Wang, Y. Protective effect of rhubarb, baicalin, and choline bitartrate on nonalcoholic fatty liver in rats. Journal of Cellular Biochemistry. 2019; 120(11), 18219-18226.

6.   Wu, L. Curcumin suppresses expression of adipogenic genes in 3T3-L1 adipocytes and high-fat diet-induced obese mice. Phytotherapy Research. 2018; 32(8), 1533-1542.

7. Li, T. Mechanisms of action of berberine and its derivatives: A review of research progress in the past decade. Pharmacological Reports. 2018; 70(5), 925-937.

Acupuncture and moxibustion improve leukopenia caused by chemo and radiotherapy

 Tiejun Tang

Leukopenia is one of the most common side effects of chemo and radiotherapy in cancer treatment. When the level of white blood cell (WBC) count is too low, chemo or radiotherapy has to be terminated to avoid fatal uncontrollable infection. If the chemo or radiotherapy plan is not completed, the remaining tumor cells will recur, leading to treatment failure. This is a difficult situation that western medicine doctors have to face in tumor treatment.

Can Chinese medicine help in this situation? The following research reports give a positive answer:

A randomized controlled trial (RCT), published in the journal Supportive Care in Cancer in 2014^[1], found that acupuncture combined with moxibustion was more effective than medication in increasing WBCs counts in breast cancer patients undergoing chemotherapy. Another study, published in the Journal of Traditional Chinese Medicine in 2012 ^[2], found that moxibustion was effective in preventing leukopenia in lung cancer patients undergoing chemotherapy.

A Meta-analysis research which Leukopenia is one of the most common side effects of chemo and radiotherapy in cancer treatment. When the level of white blood cell (WBC) count is too low, chemo or radiotherapy has to be terminated to avoid fatal uncontrollable infection. If the chemo or radiotherapy plan is not completed, the remaining tumor cells will recur, leading to treatment failure. This is a difficult situation that western medicine doctors have to face in tumor treatment.

Can Chinese medicine help in this situation? The following research reports give a positive answer:

A randomized co include 15 RCTs 1130 patients, the results showed that acupuncture can increase WBC count after chemotherapy (P <0 .00001), reduce the incidence of myelosuppression (P = 0.0002), and improve the clinical treatment effectiveness (P = 0.05). The differences were statistically significant^{. [3]}

A RCT involving 650 breast cancer patients were eligible for inclusion. Analysis by the random-effects model showed a significant effect by acupuncture of ameliorating leucopoenia during chemotherapy. Levels of WBCs were increased (P < 0.001) neutrophil counts (P < 0.001) were significantly enhanced. Moreover, regardless of the manner through which acupuncture was applied, overall values of WBCs increased. ^[4]

A Six RCTs with a total of 681 patients with various types of cancer receiving ongoing chemotherapy or after chemotherapy. The results of two RCTs suggested the effectiveness of moxibustion combined with chemotherapy vs. chemotherapy alone. Six RCTs showed that moxibustion was more effective than various types of control interventions in increasing WBC counts. ^[5]

The exact mechanisms by which acupuncture and moxibustion work to alleviate leukopenia are not yet fully understood. However, it is believed that they may help stimulate the immune system and increase the production of WBCs. They may also help reduce inflammation and oxidative stress, both of which can contribute to leukopenia.

Except acupuncture Chinese herbal medicines also can prevent and treat the bone marrow suppression caused by chemo and radiotherapy, and increase the WBCs count. I used wrote an article on this topic in 2010. ( Click the link to read more). In a recent, meta-analysis research which included of 14 RCT involving 1,053 patients the results showed that Chinese herbal medicine + chemotherapy had greater beneficial effects on WBC, neutrophil , hemoglobin and platelet counts. Compared with chemotherapy alone or western medicine + chemotherapy, Chinese herbal medicine combined with chemotherapy can effectively improve the clinical symptoms of chemotherapy-induced leukopenia^{. [6]}

It is important to note that acupuncture and moxibustion should not be used as a substitute for conventional cancer treatment, but they can be used as a complementary therapy to help alleviate side effects of chemo and radiotherapy.

In conclusion, acupuncture and moxibustion have shown promise in the treatment of leukopenia caused by chemo and radiotherapy. The combination of acupuncture and herbal medicine will lead a double effect in the clinical. The intervention of this complementary medicine therapy can often affect the prognosis of cancer treatment

References:       

1.  Lu, W.Acupuncture and moxibustion for chemotherapy-induced leukopenia: a randomized controlled trial. Supportive Care in Cancer. 2014; 22(6), 1733-1738.
2. Chen, X.Clinical observation of moxibustion in preventing chemotherapy-induced leukopenia in lung cancer patients. Journal of Traditional Chinese Medicine.2012; 32(3), 343-346.
3.  Jiayun Nian. Efficacy and safety of acupuncture for chemotherapy-induced leukopenia: A systematic review and meta-analysis. Medicine (Baltimore). 2022; 21;101(42):e30995.
4.  Ya Wen Shih. Effectiveness of Acupuncture in Relieving Chemotherapy-induced Leukopenia in Patients With Breast Cancer: A Systematic Review With A Meta-Analysis and Trial Sequential Analysis. Integr Cancer Ther. 2021 Jan-Dec;20:15347354211063884.
5. Tae-Young Choi. Moxibustion for the treatment of chemotherapy-induced leukopenia: a systematic review of randomized clinical trials. Support Care Cancer. 2015 Jun;23(6):1819-26
6.  Qing Wang. Chinese Herbal Medicine for Chemotherapy-Induced Leukopenia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials. Front Pharmacol. 2021 May 4;12:573500.

The effects of Chinese herbal medicine on cancer

 Tiejun Tang

Cancer is a leading cause of death globally, and it is estimated that one in every six deaths is due to cancer. Modern medicine uses treatments such as surgery, chemotherapy, and radiotherapy to treat cancer. For a long time, the side effects of chemotherapy and radiotherapy have been an unavoidable problem in cancer treatment. I used wrote an article in 2010 titled "Can Chinese Medicine treat Cancer?" (Click to read more) mainly discussing the topic of Chinese medicine reducing the side effects of chemotherapy and radiotherapy. Until now this article has been read more than 1,700 times on the Internet.

Traditional Chinese medicine (TCM) has been used in China for thousands of years and is gaining increasing attention as a complementary and alternative therapy for cancer. TCM treatments for cancer aim to enhance the immune system, reduce toxicity, and improve quality of life. Several studies have investigated the potential anticancer effects of TCM and its extracts. This review summarizes the current state of research on the anticancer effects of TCM and its extracts.

Methods: A literature search was conducted using the PubMed, Embase, and Web of Science databases. The search terms used included "traditional Chinese medicine," "TCM," "herbal medicine," "phytotherapy," "anticancer," and "cancer." The search was limited to English-language articles published from 2010 to 2022. Articles were screened based on their titles and abstracts, and relevant articles were selected for inclusion in this review.

Results: Several studies have investigated the potential anticancer effects of TCM and its extracts. The following TCM and extracts have been found to have anticancer effects:

1.       Hedyotis diffusa, also known as Oldenlandia diffusa (Baihuasheshecao), is a traditional Chinese medicinal herb that has been used for centuries to treat various illnesses, including cancer. Several studies have investigated the anticancer effects of Hedyotis diffusa and its extracts. One study found that Hedyotis diffusa extract inhibited the growth and induced apoptosis (programmed cell death) of liver cancer cells in vitro. The extract also inhibited the growth of liver tumors in mice. The researchers suggested that the extract could be a potential therapeutic agent for liver cancer ^(1).. Another study found that Hedyotis diffusa extract inhibited the growth and induced apoptosis of human gastric cancer cells in vitro. The extract also inhibited tumor growth in mice with gastric cancer. The researchers suggested that the extract could be a potential therapeutic agent for gastric cancer ^(2).. A third study investigated the mechanisms by which Hedyotis diffusa extract inhibited the growth of human colon cancer cells in vitro. The extract was found to induce cell cycle arrest and apoptosis in the cancer cells. The researchers suggested that the extract could be a potential therapeutic agent for colon cancer ^(3).

2.       Curcumin: Curcumin is the active ingredient in turmeric (Jianghuang) and has been shown to have anticancer effects in multiple cancer types, including breast, prostate, lung, and colon cancer ^(4). Curcumin has been found to inhibit cancer cell growth, induce apoptosis, and reduce inflammation ⁽⁵⁾.

3.       Triptolide: Triptolide is an extract from the Chinese herb Tripterygium wilfordii Hook F （Leigongteng）and has been shown to have anticancer effects in several cancer types, including pancreatic, ovarian, and prostate cancer ⁽⁶⁾. Triptolide has been found to induce cell cycle arrest and apoptosis, inhibit cancer cell migration and invasion, and reduce inflammation ⁽⁷⁾.

4.       Ginsenosides: Ginsenosides are a group of compounds found in ginseng and have been shown to have anticancer effects in several cancer types, including breast, lung, and liver cancer ⁽⁸⁾. Ginsenosides have been found to inhibit cancer cell proliferation, induce apoptosis, and reduce inflammation ⁽⁹⁾.

5.       Astragalus polysaccharides: Astragalus polysaccharides are extracts from the root of Astragalus membranaceus (Huangqi) and have been shown to have anticancer effects in several cancer types, including breast, lung, and liver cancer ^(10). Astragalus polysaccharides have been found to enhance the immune system, inhibit cancer cell proliferation, induce apoptosis, and reduce inflammation ⁽¹¹⁾.

6.       Scutellaria baicalensis: Scutellaria baicalensis (Huangqin) is a Chinese herb that has been shown to have anticancer effects in several cancer types, including lung, liver, and colon cancer ⁽¹²⁾. Scutellaria baicalensis has been found to inhibit cancer cell proliferation, induce apoptosis, and reduce inflammation ⁽¹³⁾.

Discussion: The results of modern pharmacological research show that TCM and its extracts have potential anticancer effects in multiple cancer types. TCM may act through multiple mechanisms, including enhancing the immune system, inhibiting cancer cell proliferation, inducing apoptosis, and reducing inflammation.

Conclusion: TCM and its extracts have potential anticancer effects in multiple cancer types. Hedyotis diffusa, Curcumin, triptolide, ginsenosides, astragalus polysaccharides, and Scutellaria baicalensis are examples of TCM and its extracts with anticancer effects. Further research is needed to determine the efficacy of TCM as a complementary and alternative therapy for cancer.

References:

1.  Chen J. Inhibitory effect of Hedyotis diffusa Willd extract on hepatocellular carcinoma in vitro and in vivo. Exp Ther Med. 2014;8(4):1051-1056.
2.  Li J. Inhibition of human gastric cancer cells by Hedyotis diffusa (Willd.) extract in vitro and in vivo. Pharm Biol. 2016;54(7):1155-1163.
3. Xu Y. Hedyotis diffusa Willd extract induces apoptosis via activation of the mitochondrion-dependent pathway in human colon carcinoma cells. Oncol Lett. 2015;9(5):2159-2165.
4. Cheng AL. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895-2900.
5.  Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009;14(2):141-153.
6. Wang Y,. Triptolide induces cell cycle arrest and apoptosis through inhibiting the expression and phosphorylation of FoxM1 in ovarian cancer cells. Drug Des Devel Ther. 2015;9:2399-2411.
7.  Liu Q. Triptolide and its expanding multiple pharmacological functions. Int Immunopharmacol. 2011;11(3):377-383.
8. Liu GT. Pharmacological actions and clinical use of ginseng. Chin Med J (Engl). 1989;102(12):912-922.
9. Yue PY. The angiosuppressive effects of 20(R)- ginsenoside Rg3. Biochem Pharmacol. 2006;72(4):437-445.
10. Shao BM. A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun. 2004;320(4):1103-1111.
11. Wang Y. Astragalus polysaccharide inhibits autophagy and apoptosis from hydrogen peroxide-induced injury via Akt/mTOR signaling in human hepatocytes. Biomed Pharmacother. 2017;89:827-836.
12. Choi JS. Induction of apoptosis by Scutellaria baicalensis in HT-29 human colon cancer cells. Oncol Rep. 2005;13(5):969-974.
13.  Kim DH. Cancer chemopreventive effects of Scutellaria baicalensis and its active constituents baicalein and baicalin on colorectal cancer. Biomol Ther (Seoul). 2018;26(3):255-263.