How an 1,800-year-old herbal mix heals the gut
An ancient Chinese formula might ease side effects of cancer treatments.
An age-old mixture of four herbs could spare patients with cancer some of the side effects of chemotherapy.
The cocktail comprises Chinese peony, Chinese liquorice, the fruit of the Chinese date tree and flowers of the Chinese Skullcap plant. In China, they call it ‘Huang Qin Tang‘ we’ll call it HQT and they have used it to treat gastrointestinal problems for about 1,800 years.
The blend HQT (aka ‘PHY906’) , and shown in early clinical trials that the mix can combat the severe diarrhoea caused by many chemotherapy drugs, which destroy fast-dividing gut cells in addition to tumour cells.
Now, researchers at Yale University School of Medicine, both in New Haven, Connecticut, have some early leads on how HQT does this, despite the fact that most of its individual chemical components remain unknown.
HQT still needs to prove itself in larger clinical trials. In 2004, the US Food and Drug Administration (FDA) eased regulations on herbal mixtures, allowing the approval of medicines that have been proved to be safe and effective, even if their individual components aren’t known.
“This is a new paradigm of drug development,” says Dr Yung-Chi Cheng, a pharmacologist at Yale. “It’s a typical example of West meets East.”
Divide and conquer
The latest results for HQT , which provide molecular details indicative of how it might repair chemotherapy-damaged guts, the results are published online today in Science Translational Medicine1.
The etiology of these complex syndromes and illnesses is not singular; they are caused by many different genetic and environmental factors,” Cheng said. “Thus, it is impractical to [have a singular focus] as we pursue solutions.” ~ Dr Yung-Chi Cheng (2015)
When mice receive a dose of the chemotherapy drug irinotecan, which blocks an enzyme, called topoisomerase, that is important to DNA replication, their gut cells begin to die off. However, a dose of HQT given with the chemotherapy restored these cells within four days, Cheng’s team found. The guts of mice taking the herbal medicine contained fewer dying cells and more dividing cells than those of control animals.
HQT, reduces gastrointestinal toxicity and enhances the anti-tumor effect of some anti-cancer drugs. HQT unblocks an enzyme called topoisomerase, which alters the supercoiled form of a DNA molecule and is important to DNA replication, it is blocked by some chemotherapy drugs and if blocked the gut cells begin to die off.
The researchers measured the activity of genes in the gut cells of mice on HQT and irinotecan and found that genes in the Wnt pathway, which encourages progenitor cells in the gut to divide, were upregulated.
But ramping up the gut’s stem cells isn’t the only way that HQT combats diarrhoea, Dr Cheng says. Irinotecan also causes inflammation, which the herbal medicine seems to prevent. The guts of mice on HQT contained fewer inflammatory immune cells called macrophages than did those of rodents on chemotherapy alone, and the activity of three genes linked to inflammation — Cox2 (PGE-2), NF-κB and iNOS — were also down.
Inflammation Drives Cancer, HQT Reduces 3 Major Inflammatory Enzymes
Cheng thinks that HQT ‘s multitude of effects can be explained through its different chemical constituents, and hopes that his team can identify which chemical is responsible for which change. “This will eventually simplify the procedures used for quality control,” he says.
All three major inflammatory pathways in the body seem to be affected by the presence of HQT, suggesting that the herbs have multiple sites of action within the body. By addressing all three pathways Cox2, NF-KB and iNOS, the results of HQT are better than any anti-inflammatory drug on the market today” ~ Dr Yung-Chi Cheng
Cheng’s team are 6 years into Phase II clinical trial results for HQT and are going through FDA approval for their PHY906 version.
HQT is one of the most well studied Chinese formulas. There are 114 studies on pubmed alone and yet it is still not widely available. So how does it do it’s magic on the Gut and Colon? This next study will hopefully explain.
The mainstays of current IBD treatments involve the use of corticosteroids, immunomodulators, and biologic agents targeting specific cytokines. Although these drugs are conventional therapeutics, most of these treatments are still being used with reluctance due to the high cost, toxic side effects, and uncertainty about long-term safety [8–10]. Consequently, many patients turn to alternative strategies, including traditional plant-based remedies.
HQT has been used for nearly 1800 years in traditional Chinese medicine to treat common gastrointestinal distress, such as diarrhoea, abdominal spasms, fever, headache, vomiting, nausea, extreme thirst, and subcardiac distention .
Although HQT is also significantly protective in the treatment of IBD in Chinese clinical application, further clinical evidence and definitive mechanisms of action that demonstrate the role of HQT in gastrointestinal diseases are still lacking.
In 2015 the National Natural Science Foundation of China, setup a study to investigate the contribution of HQT to the amelioration of colitis and CD4+ T cells immune homeostasis in 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced acute colitis. TNBS is a particularly nasty substance , it is an extremely toxic oxidant, corrosive to metal and skin, irritant and explosive when dry, so it’s a pretty extreme test.
Huang Qin-Tang (HQT) as a classic traditional Chinese herbal formulation is widely used to ameliorate the symptoms of gastrointestinal disorders, including inflammatory bowel disease (IBD). The study was designed to investigate the therapeutic potential and immunological regulatory activity of HQT in experimental colitis in rats.
Using an animal model of colitis by intrarectally administering 2,4,6-trinitrobenzenesulfonic acid (TNBS), they found that administration of HQT significantly inhibited the severity of TNBS-induced colitis in a dose-dependent manner. In addition, treatment with HQT produced better results than that with Mesalazine, as shown by improved weight loss bleeding and diarrhoea scores, colon length, and intestinal inflammation.
The Anti-Inflammatory Potency of HQT shown as Superior to Mesalazine in the TNBS-Induced Colitis Model
Oral administration of Mesalazine is the first-line approach to induce and maintain clinical remission in patients with mild-to-moderate Colitis or Crohns disease .
To further assess the severity of colitis, colon length was measured in each group of rats. Colons of rats treated with TNBS alone were on average 10% shorter than those of rats subjected to additional treatment with HQT or mesalazine (Figure 2(d)). This inflammatory phenotype was further evidenced by the gross and microscopic appearances of the colon. Consistent with the clinical parameters discussed above, treatment with HQT or mesalazine significantly ameliorated the macroscopic scores compared to rats treated with TNBS alone.
Administration of HQT or mesalazine prevented the induction of these inflammatory cytokines , suggesting that HQT treatment might have broad anti-inflammatory activity. Together, these results clearly indicate that HQT plays a therapeutic role and is superior to Mesalazine in resolving the inflammatory response following TNBS-induced injury of the colon.
As for potential immunological regulation of HQT action, the percentages of Th1 and Th17 cells were reduced, but those Th2 and Treg cells were enhanced in LPMCs after HQT treatment. Additionally, HQT lowered the levels of Th1/Th17-associated cytokines but increased production of Th2/Treg-associated cytokines in the colon.
Their results indicated that HQT plays an important role in the regulation of intestinal immune responses in TNBS-induced colitis by downregulating effector phenotype of Th1 and Th17 cells, while promoting Th2 and Treg responses. Thus, using HQT, a Chinese medicinal formulation, to regulate immune homeostasis may offer a promising alternative to a current therapeutic strategy for IBD. [pubmed PMC453942]
Werone have developed our own version of HQT as an alcohol extracted tincture. Whilst researching the properties of Scutellaria Baicelansis it has been proven that hydrophobic flavonoid-induced apoptosis is most effective, so Ligusticum (Lovage Root) has been added to the HQT formula.
You can find our HQT Tincture here.
Nutraceutical DisclaimerThese statements have not been evaluated by the Food and Drug Administration and the items are not intended to diagnose, treat, cure, or prevent any disease nor are they associated, endorsed, affiliated or sponsored by Anthony William or Medical Medium®.
5) East Meets West in Cancer Treatment: Ancient herbal remedies prove their worth in modern clinical trials
6) Effect of PHY906 on capecitabine (CAP)-induced diarrhea in patients with GI malignancies
7) Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy
8) Huangqin-Tang Ameliorates TNBS-Induced Colitis by Regulating Effector and Regulatory CD4+ T Cells