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More herbal remedies for cancer

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*Researchers find how catnip, ginger, cloves, cannabis beat disease
*Brussels sprouts, green tea convert breast tumour to treatable form
*Scientists to produce therapeutic drugs in yeast using local plants

Scientists have validated more natural remedies for the treatment of cancer.New research has given scientists a big clue about how catnip (Nepeta cataria) may help humans deal with cancer and how it produces intoxicating chemical, called Nepetalactone, as well as how it gets cats high. The scientists believe that catnip, once reserved for cats, could serve as a worthwhile case study that may help humans deal with cancer.

The study was conducted by researchers at the Norwich-based John Innes Centre and published Monday in scientific journal Nature Chemical Biology. Catnip contains a compound called Nepetalactone, which is part of a class of chemicals referred to as terpenoids. Ginger, cloves and cannabis are also considered a terpene.

Nepetalactone does not affect all cats, but it does stimulate many of them – several studies have shown that two-thirds are susceptible to the effects of catnip.

The mint family also contains terpenes, but catnip produces them in a completely different way. A major difference is that usually in plants, such as peppermint, a single enzyme forms terpenes, John Innes Centre explained. The mint family also contains terpenes, but catnip produces them in a completely different way. In catnip, enzymes in a two-step process form terpenes

“We have made significant progress in understanding how catnip makes nepetalactones, the chemicals that sends cats crazy,” Benjamin Lichman, who led the study, said in a statement. “Catnip is performing unusual and unique chemical processes, and we plan to use these to help us create useful compounds that can be used in treatment of diseases such as cancer.

“We are also working to understand the evolution of catnip to understand how it came to produce the cat-active chemicals,” he added. Another study published in the journal Oncotarget suggest that catnip may provide the novel cure for lung cancer.

Non-small cell lung cancer (NSCLC) is regarded as one of the major intractable diseases, which was cured mainly by chemotherapeutics in the clinical treatment at present. But it is still a vital mission for the current medical and researchers that hunting a natural medicine which have little side effects and high-efficiency against the NSCLC on account of the shortcomings on current drugs.

The Chinese researchers noted: “Nepeta cataria plays an important role in anti-cancer treatment according to the reports which was recorded in the Chinese Pharmacopoeia of version 2015 and belongs to one of the Traditional Chinese medicine (TCM). Microfluidic chip technology is widely used in scientific research field due to its high-throughput, high sensitivity and low cost with the continuous progress of science and technology. In this study, we investigate the effect of total flavonoid extracted from Nepeta cataria L. (TFS) through human lung cancer cell line A549 based on the microfluidic device and Flow Cytometry. So we detected the mRNA expression of MicroRNA-126 (miR-126), VEGF, PI3K, PTEN and proteins expression respectively to explore the partial PI3K-AKT pathway molecular mechanisms through Quantitative Real-time PCR (qRT-PCR) and Western Blot.

“The results showed that TFS could disturb the expression of miR-126 and regulate the PI3K-AKT signaling pathway to meet the effect of anti-cancer. Taking all these results into consideration we can draw a conclusion that TFS may be used as a novel therapeutic agent for NSCLC in the near future.”

The study is titled “Mechanism of modulation through PI3K-AKT pathway about Nepeta cataria’s extract in non-small cell lung cancer.”Meanwhile, researchers at the University of Alabama at Birmingham (UAB) have found a dietary combination that transforms the most lethal of all breast cancers into a highly treatable breast cancer. Specifically, scientists involved in the Scientific Reports study say sulforaphane – from cruciferous vegetables such as broccoli sprouts – along with polyphenols from green tea may be the key.

Epigenetics – the study of biological mechanisms that will switch genes on and off – are used by Trygve Tollefsbol, Ph.D., Professor of Biology in the College of Arts and Sciences and Senior Scientist at the Comprehensive Cancer Center and Yuanyuan Li, M.D., Ph.D., a Research Assistant Professor of Biology, as a mechanism to identify ways we can change human gene expressions in fatal diseases, including breast cancer.

All breast cancers are either estrogen receptor-positive (ER-positive) or estrogen receptor-negative (ER-negative), the UAB press release explains. The tumors in ER-negative breast cancer are much less likely to respond to hormone therapy than are tumors that are ER-positive, which means that ER-negative breast cancers are typically very aggressive.

“Unfortunately, there are few options for women who develop ER-negative breast cancer,” Tollefsbol says. “Because of the poor prognosis this type of cancer carries, new advances in prevention and treatment for ER-negative breast cancer have particular significance.”Tollefsbol and fellow researchers set out to further research how scientists can efficiently neutralize mechanisms that lead to, and worsen, ER-negative cancers. Up until now, conventional cancer prevention has focused primarily on single chemopreventive compounds.

“One reason many in the field shy away from combining two or more compounds at a time for treatment research is the fear of adverse effects and potential interactions that are unknown,” Tollefsbol says.

“To overcome that concern, we chose compounds that we felt confident would interact well together because they have similar favorable biological effects but still have different mechanisms for carrying out these effects that would not interfere with one another,” adds Tollefsbol.

Tollefsbol and his team identified two compounds in common foods that are known to have success in cancer prevention, and that could potentially be combined to successfully “turn on” the ER gene in ER-negative breast cancer so that the cancer could be treated with estrogen receptor inhibitors such as tamoxifen.

“One way we can use epigenetics as a powerful tool to fight cancer is through compounds found in our everyday diet,” Tollefsbol says. “Vegetables, for example, are filled with these types of compounds. Your mother always told you to eat your vegetables, and science now tells us she was right.”

Another compound found in green tea has been shown to stimulate epigenetic changes in cancerous genes, according to prior studies from Tollefsbol’s lab.These compounds, used in the right way, can help modulate gene expression aberrations that are contributing to the disease.

The researchers found that a combination of dietary plant-derived compounds consisting of sulforaphane from cruciferous vegetables such as broccoli sprouts, along with polyphenols from green tea, is successful in preventing and treating ER-negative breast cancer in mice that are genetically programed to develop ER-negative breast cancer at high rates.

Further investigation revealed that the mechanism for the efficacy of these two dietary compounds involved epigenetic changes induced in the ER gene regulatory region.With the combined dietary treatment the researchers administered, the tumors in the mice were converted from ER-negative to ER-positive cancers. This rendered the breast cancer easily treatable with tamoxifen, an estrogen receptor inhibitor.

“The results of this research provide a novel approach to preventing and treating ER-negative breast cancer, which currently takes hundreds of thousands of lives worldwide,” says Li. “The next step would be to move this to clinical trial, and to eventually be able to provide more effective treatment options for women either predisposed to or afflicted with this deadly disease.”

Also, nature is so complex that natural molecules used for cancer treatment still cannot be produced by chemical synthesis. Today, major chemical and pharmaceutical companies harvest large amounts of rare plants and seeds in order to extract valuable substances.But the production methods based on extracts from natural resources are environmentally damaging and often give rise to extensive piles of chemical waste. In addition, there is a great danger that these rare plants will go extinct.

The need to find new and more sustainable production methods for these types of medicines has grown since the United Nations (UN) recently adopted new regulations to protect biodiversity and raw materials in third world countries.“With these new rules, a real alternative is needed if we wish to be able to produce therapeutics to cancer patients or people suffering from mental illnesses in the future,” says Senior Researcher at The Novo Nordisk Foundation Center for Biosustainability. He is the coordinator of a new big EU Horizon 2020 project called MIAMi, which has just received a grant of 6 million Euro.

Indian snakeroot may be the solution. In many cases, these very complex plant chemicals can’t be synthesized chemically like ‘normal’ pharmaceuticals — it simply has to be a bio-catalytic process.The aim of the MIAMi research project is to provide the pharmaceutical industry with an alternative production route using the cellular workhorse baker’s yeast. To start with, the researchers want to map the so-called biosynthetic pathways of the rare plant Rauvolfia serpentina with the common name Indian snakeroot.

From traditional Chinese medicine, it is known that Indian snakeroot produces molecules with anticancer effect. However, manufacturing the valuable compounds outside the plant is still not possible, because the biosynthetic pathways are unknown.In short, a biosynthetic pathway is a number of specific genes that code for enzymes, which synthesize a bio-molecule within the cell. Knowing the genetic “route” of the product makes it possible to move the genes into, for instance, baker’s yeast. The goal is to insert the genes into yeast cells that will act as biological cell factories capable of producing large amounts of these specific therapeutic substances.

One of the partners of MIAMi is the French chemical company Axyntis, which annually imports hundreds of tonnes of plant seed to extract substances for further production of medicine such as tabersonine from the rare plant Voacanga africana. However, the new legislation limits this way of producing medicine.

“The industry knows that they need to change, which these regulations are also a clear signal about. We do not expect to be able to manufacture the products within this project period so that they can compete with current processes, but the alternative is that companies in the future can’t offer the same products to their customers,” says Michael Krogh Jensen.

Over the past 20-30 years, the shelves of bioactive substances in the company’s “chemical libraries” have gradually been used up, and the industry is now in great need of new drugs against new and existing diseases. Therefore, there is also a need to discover new natural occurring molecules with activity against some of the major public diseases such as cancer and mental illness, for example, schizophrenia. Another focus is, therefore, to find new and unknown plant molecules. The project runs for a four-year period.

Interestingly, a local version of Rauvolfia serpentina, Rauvolfia vomitoria, commonly called Chieftaincy leaf, serpent wood or swizzler stick in English, asofeyeje in Yoruba, akanta in Ibo, and wada in Hausa, has been validated for treatment of ovarian, pancreatic and prostate cancer.

Until now, Rauvolfia vomitoria also spelt Rauwolfia vomitoria has been used to boost the immune system against diseases, treat prostate problems including cancer, diabetes, mental illness and pain.

Indeed, herbal preparations of Rauwolfia vomitoria, a tropical shrub in the family of Apocynaceae, have been used in traditional folk medicine in Africa to treat a variety of ailments including fever, general weakness, gastrointestinal diseases, liver diseases, psychosis, pain, and cancers.

Several studies have shown that extracts from this plant are enriched in carboline alkaloids and indole alkaloids. Many of these alkaloids have been isolated from the stem, leave, and root of Rauwolfia vomitoria. From the root alone, there are mainly five types of more than 20 alkaloids identified.

Researchers have isolated reserpine, a drug to control high blood pressure and relieve psychotic symptoms, from the root bark of Rauwolfia vomitoria. Other reported activities of the isolated compounds mainly affect the neurological and cardiovascular systems, with many of them not studied for their bioactivities.

The anticancer activities of these components have barely been studied. One early study in 1986 suggested anti–lymphoma ascites cells effects of three alkaloids, alstonine, serpentine, and sempervirine, in specific conditions.

Another study in 2006 reported on the anti–prostate cancer activity of Rauwolfia vomitoria, but the active anticancer component in the extract was not known. Apart from the investigations of its components, the extract as a whole is widely used and actively studied.

The extract of this medical herb as a whole mixture has been a traditional medicine for more than 2000 years in Africa for the treatment of hypertension and mental disorders. The effectiveness has been confirmed in more recent studies to be mainly as antipsychotic, antihypertensive, anti-inflammatory and improving blood chemistry.

A Rauwolfia-citrus tea is in an early phase clinical trial in Denmark for its anti-diabetic effect.But a more recent study published in BMC Complementary and Alternative Medicine, The official journal of the International Society for Complementary Medicine Research, has validated extracts from two medical plants Pao Pereira (Pao) and Rauwolfia vomitoria (Rau) for their anti-tumor effects in various types of pancreatic cancers and ovarian cancers.

The researchers concluded: “…These results pave the way for in vivo studies of the anti-cancer effects of Rauwolfia vomitoria and Pao Pereira extracts, especially in gemcitabine-resistant pancreatic cancers and carboplatin-resistant ovarian cancers. Studies on mechanisms of the anti-cancer actions are also undergoing concerning apoptosis and cell cycle arrests.”


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