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Pien Tze Huang orally disintegrating tablets

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Traditional Chinese	片仔癀
Literal meaning	"heat toxin [and] swelling or pain"
Transcriptions Standard Mandarin Hanyu Pinyin Piànzǎihuáng

Pien Tze Huang (片仔癀; Piànzǎihuáng) is a traditional Chinese herbal formula first documented during the Ming Dynasty and historically used to combat inflammation. In recent years it has been tested on animals for its benefits against various diseases such as multiple sclerosis, cerebral ischemia, carbon-induced liver damage, and cancer.

Side effects have yet to be seen as PZH has not yet been clinically tested. However, it is commonly sold as oral tablets taken daily (for general health) or as a pearl cream (for acne and freckles), and no side effects have been reported.

Current production

The sole manufacturer of Pien Tze Huang is the Zhang Zhou Pien Tze Huang Pharmaceutical Company Limited, China. The prescription and technology have been classified as state secrets, and the medicine has won the National Gold Award and passed the Country-of-Origin Marking certificate. Additionally, it was ranked #1 in the top 5 exported Traditional Chinese medicines in 2014, and top 10 enterprises in the Traditional Chinese medicine industry in 2015.

The Zhang Zhou PZH Pharmaceutical Company markets Pien Tze Huang as "relieving internal heat and deleting toxin, dispelling stasis and easing pain, stopping bleeding and reducing sores. Used for internal, external or mixed hemorrhoids." In addition to PZH, the company sells other traditional Chinese medicines in the form of pills or cream, cosmetics, health food, and medical apparatus.

Traditional uses

Pien Tze Huang (PZH) was developed in 1555 A.D. by a court doctor to treat cancer, diseases in the liver, and general pain and swelling. According to the Zhang Zhou PZH Pharmaceutical Company, research on the history of Pien Tze Huang has produced the tale of a royal physician who fled the imperial court with the recipe for PZH, using it to cure scores of locals and increasing its renown as an 'almighty medicine'.

Its primary ingredients are musk, ox gallstone, snake gall, and Tienchi, all of which have anti-inflammatory, immunoregulatory, and neuroprotective effects. It has been used as a folk remedy to combat cancer, as it reduces inflammation, decreases temperature, and detoxifies.

It is commonly taken via oral capsules for its anti-inflammatory benefits and help with stomach pains, or used as cream for skin lightening and acne.

Modern research

Many modern studies have examined how PZH might be used for treatments of various different diseases in cells, mice, and rats. No clinical trials or studies on humans have so far been performed. A few studies on PZH's effect on model organisms with multiple sclerosis, cerebral ischemia, carbon-induced liver damage, or cancer are below.

Multiple sclerosis

Current treatments for MS are often highly toxic and have many adverse side effects. As a natural alternative to the current treatment procedures, researchers considered PZH, and trials were performed on rats to test its efficacy. Male Lewis rats with multiple sclerosis were treated with three doses of PZH. Their symptoms, inflammatory levels, protein levels, tissue features, and organs were monitored, and results showed a decrease in clinical severity and infiltration of inflammatory cells. Overall, PZH had a positive effect on the MS symptoms, and in such a low dose, no toxicity was observed and the mice exhibited no adverse effects. These results caused the authors to conclude that PZH may be a viable candidate for a natural MS treatment; however, further trials need to be conducted on humans before this claim can be verified.

Carbon tetrachloride-induced damage

Carbon tetrachloride (CCl₄) is an environmental pollutant released into the air, water, and soil from factory byproducts. It is also used to make refrigerants, aerosols, pesticides, electrical equipment, and industrial-strength adhesives. Breathing air or drinking water contaminated with CCl₄ can cause liver damage, and has been linked to liver cancer.

PZH was tested for its protection of the liver from carbon tetrachloride‐induced damage in mice. Randomly bred young mice were injected with carbon tetrachloride and then treated four times with PZH over 60 hours, after which their livers were removed and analyzed. One test examined plates of hepatocytes for cells degenerating from CCl₄ treatment. The test group treated only with CCl₄ showed significant liver cell damage. The livers from the mice treated with CCl₄ and PZH were significantly less damaged. An additional analysis showed that PZH increases the responses of signal pathways. These test demonstrate that PZH can protect the liver from hepatotoxicity and allow it to function despite CCl₄-induced damage.

Cerebral ischemia and stroke

Cerebral ischemia is a condition where the brain is receiving too little blood to properly function, leading to poor oxygen supply and therefore tissue death or ischemic stroke. A hypertensive stroke occurs when blood pressure becomes too high (hypertension) and is the most common form of stroke. As currently there are few effective treatments available for ischemic or hypertensive stroke, the following study examined the neuroprotective effects of PZH. Spontaneously hypertensive rats (SHRs) were either treated with PZH until a stroke occurred, then given saline, or solely given saline throughout the duration of the experiment. The rat cells were tested and showed that the rats treated with PZH had decreased stroke-caused cell death in the hippocampus and cerebellum, demonstrating that PZH can help protect brain tissue from death.

Cancer

• Ovarian cancer cells: Ovarian cancer is the fifth most fatal form of cancer among women, killing about 15,000 per year. While there is a 92% survival rate if the cancer is found before it spreads, only 15% of all ovarian cancers are found at that early stage, and alternative forms of treatment are constantly being researched. Considering PZH as a possible alternative cancer treatment, this experiment tested the effect of PZH on ovarian cancer cells outside of the body. First, an MTT assay, assessing cell metabolic activity, was performed to view the effect of PZH on OVCAR-3 cancer cells and their digestions. Secondly, a Transwell assay was executed to see if PZH caused endothelial cell migration, and staining and flow cytometry (the measurement of cell characteristics) to check for apoptosis frequency and cell cycle changes. The results were that PZH inhibits proliferation, invasion, and migration of OVCAR-3 cancer cells, decreasing cancer's ability to self-replicate and reproduce and therefore decreasing the effects of cancer in the body overall. However, it has no effect on cancer cell apoptosis. The study indicated PZH affects the AKT-mTOR pathway, therefore inhibiting cancer cell production but not increasing cancer cell death.

• Angiogenesis in vivo and in vitro: Preventing cancer from replicating and therefore from spreading is one effective technique to fighting the disease. Without an effective 'food supply' in the form of blood vessels, the cancer cannot properly feed and reproduce. To examine the effects of PZH on angiogenesis (the development of new blood vessels) this study treated human umbilical vein endothelial cells (HUVECs) with different levels of PZH over different amounts of time. To evaluate in vivo and in vitro effects, live chicken embryo membranes and an ECMatrix gel system containing extracted HUVECs were used. The results of the study showed that both in vivo and in vitro, PZH inhibits angiogenesis. The total number of blood vessels in chicken embryos significantly decreased when treated with 0.5 mg of PZH, and the ECMatrix gel showed that HUVECs treated with PZH caused a decrease in capillary tube formation. Since tumor growth requires angiogenesis in order to gain nutrients, grow, and spread, inhibition of angiogenesis is a very viable way to combat tumor growth. While most anti-angiogenic agents are toxic and cannot be used in long-term increments, PZH is a natural product that has been gaining medical interest for its ability to combat angiogenesis with ideally less side effects than chemical treatments.

• Colorectal cancer: The effects of PZH on tumor angiogenesis have also been tested in a mouse model of colorectal cancer. Male mice were injected with cells to begin tumor growth and then treated with PZH over 3 weeks. The tumor tissue analysis evaluated tumor weight and volume between the control and experimental group, and showed that tumor growth was suppressed by PZH treatment, decreasing the volume and weight by around half. Further analysis showed that the PZH was inhibiting tumor angiogenesis by interfering with signaling pathways, showing that pathway suppression is most likely one mechanism by which PZH inhibits cancer growth.

• Cell proliferation: In a related study to the one above, PZH was tested for its effects on the signal transducer transcription 3 (STAT3). STAT3 is critical for cell proliferation, and is commonly activated along with the development of many types of cancer. This experiment tested male mice with colorectal cancer for tumor growth and examined the change in STAT3 phosphorylation. The results showed that PZH treatment decreased the activation of STAT3, inhibited cancer cell proliferation, and generally inhibited tumor growth.

Side effects

A case of drug-induced pneumonia caused by Pien Tze Huang has been reported.

With many traditional Chinese herbal medicines the short-term side effects of headache, nausea or mild gastrointestinal symptoms are frequently seen, although there is little data or statistics due to the lack of research and information.

Notes and references

Category:Traditional Chinese medicine pills