A sound alternative medicine?

DOST develops guyabano-derived wellness products


THE debates have been fierce and challenging; they rouse one from the dark blankness brought about by this debilitating disease.

“We don’t call it by its real name,” a mother softly whispered. “We prefer to call it as the Big C,” referring to liver cancer which her son has. Nena (not her real name) is one of thousands of sad witnesses to its crippling effects.

“It saps your spirit and strength; it leaves you hopeless and crying like a child,” the 55-year-old fish vendor continued, slowly getting teary-eyed. “You know, we have tried everything. With our money fast running out, it’s a relief to know that guyabano tea can help.”

Mounting the evidences for folk medicine

Medical practitioners in the country have categorized the use of tea from decocted guyabano (Annona muricata L.) leaves as folk medicine.

Denounced in an October 2013 interview with a national newspaper as “scientifically unsupported alternative cancer treatment,” a medical group has kept to its side of the fence.

However, did you know that traditional medicine, also called folk medicine or alternative medicine, has since been and still is being practiced the world over?

Comprised of knowledge systems that herbalists and/or divine healers have developed over generations within various societies, it traces its roots to the time before the era of modern medicine.

The World Health Organization (WHO) defines alternative medicine as “the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illnesses.”

In some developed countries like South Korea, China, and Taiwan their nationals jointly patronize their modern medicine and alternative traditional medical practices.

The South Korean government, for one, established a national school of traditional Korean medicine in 2008, more than 5,000 years after the establishment and use of ancient Korean medicine. Called the School of Korean Medicine, it is situated inside Pusan National University.

There are other Asian and African countries where up to 80 percent of the population relies on traditional medicine for their primary health care needs.

In fact, core disciplines, which study traditional medicine, include herbalism, ethno medicine, ethnobotany, and medical anthropology.

The WHO cautions, however, that “inappropriate use of traditional medicines or practices can have negative or dangerous effects” and that “further research is needed to ascertain the efficacy and safety” of several of the practices and medicinal plants used by traditional medicine systems.

Thus, there is need to draw a line between alternative medicine and quackery.

Tracing the roots

So what is the buzz? What is the contention about this green, heart-shaped fruit with a waxy, leathery peel and soft, pliable spines?

It is, actually, about its decocted leaves, which many enterprising “herbalists” peddle as a cure-all, especially for the Big C.

Several groups have in fact exchanged words regarding their beliefs about guyabano’s medicinal uses.

For cancer patients, their physical ordeal is made more difficult by the many doubts and aspersions cast by some quarters about their “natatanging gamot sa aking sakit (my only cure for my sickness).”

Thus, it might surprise some to know that a message by Dr. Gordon Cragg during the 38th Annual Meeting of the American Society of Clinical Oncology in 2002 stated that approximately 62 percent of commercially available drugs have in fact natural product origins.

Former chief of the Natural Products Branch of the National Cancer Institute Developmental Therapeutics Program in Bethesda, Maryland, Dr. Cragg championed the preservation and study of plants, since they are the source of chemical compounds that form the basis of many therapeutic drugs.

He said, “These natural products in fact play important roles as direct treatments, as templates, or as lead compounds that are modified for the treatment of human diseases.”

He continued that the commonly known example from folkloric medicinal plants is the anticancer agent paclitaxol from Taxus brevifolia (locally known as Pacific yew or western yew) discovered by Wall and Wani in 1971. Treatment of advanced ovarian cancer now uses this.

Other examples of anticancer drugs derived from natural products include camptothecin from Camptotheca acuminata (happy tree, cancer tree, tree of life); podophyllotoxin from Podophyllum peltatum (may-apple); vincristine and vinblastine from Vinca rosea (periwinkle); and Adriamycin from the bacteria Streptomyces peucetius.

These have encouraged pharmaceutical chemists to search for new drugs from medicinal plant sources.

The latest to create such passionate debates is guyabano, a natural medicine containing acetogenins. A class of polyketide found in plants of the family Annonaceae, acetogenins specifically in Annona muricata have been cited by cytotoxicity (study of compounds toxic to cells) researchers, namely, Graver et al. (1992), Rieser et al. (1993), Li et al. (1994), and Alali et al. (1999), among others, as having potent anticancer properties.

Building the blocks

In 1997, Nicholas H. Oberlies, Vicki L. Croy, Marietta L. Harrison, and Jerry L. McLaughlin of the Department of Medicinal Chemistry and Molecular Pharmacology in Purdue University, Indiana published in the magazine Cancer Letters, results of their study entitled “Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay.”

With the anti-cancer properties of acetogenins fully established, they worked on the capability of acetogenins to block, or inhibit cell growth of tumor cells. They tested these on several cell types in vitro (outside their normal biological context such as in glass or petri dishes) using cancerous cells from mice and humans as well as non-cancerous cells from the intestinal tract of rats.

Results showed that acetogenins applied to cancerous cells blocked their growth.

However, it did not affect non-cancerous and healthy cells and did not block their growth. These findings indicated that acetogenins selectively blocked cell growth of tumor cells, while keeping healthy cells unaffected.

Now those are certainly exciting and good news. Na Nena has reason to celebrate.

There have been more than 40 annonaceous acetogenins isolated from the stems, leaves, and seeds of guyabano.

In the 1994 study of annonaceous acetogenins also from guyabano, Li et al. found three annonaceous acetogenins from the extract of the stem bark, namely, muricatin A, muricatin B, and muricatin C.

In those annonaceous acetogenins, four known compounds, muricatetrocin A, muricatetrocin B, corossolin, and corossolone, show special selective cytotoxicities against hepatoma (liver cancer) cell lines Hep G2 and Hep G2.2.15.

In 2007, Yang-chang Wu of Kaohsiung, Taiwan received US Patent No. 7223792 for his work on “Cytotoxic annonaceous acetogenins from Annona muricata,” which include seven newly discovered pure compounds for curing human tumor. These are muricin A, muricin B, muricin C, muricin D, muricin E, muricin F, and muricin G.

However, documented efforts to produce large amounts of these active ingredients in the acetogenins of guyabano and subject these to clinical trials involving humans, have been few.

For the meantime, one can turn to the biological acetogenins found in the guyabano natural supplement in capsule and teabag produced by the Department of Science and Technology’s Industrial Technology Development Institute (DOST-ITDI).

Nature in convenient bag and capsule

Remaining undaunted by the “talk” and doubts of some on the therapeutic effects of decocted guyabano leaves, Dr. Rosalinda C. Torres, supervising science research specialist at the Chemicals and Energy Division of ITDI, stood firm in her belief.

For years, she and her team of 10 researchers persisted in the daily research chore until finally proving to all that they can do it.

On October 24, 2014, Epifanio M. Evasco, director of patents of the Intellectual Property Philippines-Bureau of Patents (IPP-BP), awarded Dr. Torres and her team Utility Model Patent Registration Nos. 2-2014000346 and 2-2014000347 for their work on the process of preparing guyabano leaves in capsule and teabag, respectively.

Her team members are Carmelita O. Manalo, Teresita S. Bonifacio, Evelyn B. Manongsong, Elvira L. Arrogante, Romulo R. Estrella, Eduardo A. Lanto, Cynthia N. Ochona, Yolanda C. Paras, Juliet T. Barcala, and Regin Glen Ortiz.

Two weeks later, IPP-BP again awarded the group with Utility Model Patent Registration Nos. 2-2014000307 for the process of preparing guyabano fruit in capsule, and 2-2014000308 for guyabano fruit in teabag.

The patent will allow the team to make, use, sell, or import the four utility models for the next seven years.

Following the WHO standard protocol, “We processed the fruits and leaves of guyabano and performed thin layer chromatographic fingerprinting and phytochemical screening,” Dr. Torrres said. These analytical techniques allow detection of all main and single, low-molecular constituents of a plant drug.

“We did not stop there,” she continued. “We went deeper and determined the potency of the extracts to inhibit microbial activities of the following disease-causing strains:

• Staphylococcus aureus, bacteria that cause boils, impetigo, food poisoning, cellulitis, and toxic shock syndrome;
• Escherichia coli, bacteria that can cause serious food poisoning;
• Trichophyton mentagrophytes, fungal parasites that cause infection of hair, skin, and nails;
• Candida albicans, a causal agent of oral and genital infections it has emerged as an important cause of illnesses and fatality in patients suffering from AIDS, undergoing cancer chemotherapy, and organ or bone marrow transplantation; and
• Fusarium moniliforme, which can cause corneal ulcers.”

Other prominent tests conducted by the team focused on establishing the anti-inflammatory and anti-diabetic properties of the extracts as well as their acute toxicity levels.

Meanwhile safety assessments of the guyabano leaves and fruits indicated pesticide residues and heavy metal content that are within the reference limits.

What’s inside?

Past the green, waxy, leathery peel of guyabano is milky white, cottony flesh.

Dr. Torres’ team, however, favored unripe fruits.

These contain flavonoids while the leaves contain tannins, fats and oils, unsaturated steroids and triterpenes, and flavonoids.

“We analysed the potency of leaf extracts against the control of edema (swelling) which may assist suffering patients. At 500 mg of guyabano capsule per kilogram of body weight, a patient may expect a 67 percent protection from swelling,” she explained.

“What was so encouraging for us, though, were our findings regarding the antidiabetic effects of the extract when compared against the positive control Metformin (a medicine used to control blood sugar levels in type 2 diabetics).”

Cautioning readers, she stressed, “There are certainly aspects of our research products that still need refining. Clinical trials are the next order of the project. Accelerated tests to determine the longterm effects of the same on microbial activity of cited microorganisms, as well as, their inhibitory properties against viruses, carcinogens, and allergens are also crucial.”

Other wellness products

To date, Dr. Torres’ team has developed other wellness products including essential oils used mainly for their aroma-giving properties. Through steam distillation, oil to be extracted from freshly harvested dried parts of aromatic plants like flowers of ylang-ylang and sampaguita, leaves of citronella, eucalyptus, and lemon grass, and calamansi rind, among others.

She elaborated that industry uses these in aromatherapy, “…for food and beverage processing, and in production of perfume, cosmetics, and other personal care products.”

Another of their products is a slimming cream derived from caffeine from coffee grounds and grapefruit oil extract. It has significantly reduced weight, waist, and hip measurements, as confirmed by an eight-week clinical trial.

Meanwhile, two other research teams from ITDI have developed a candle-type ceramic water filter and a salt iodization machine.

Led by Dr. Blessie A. Basilia, head of the materials science division, local pottery makers now fabricate a candle-type ceramic water filter from clay, sand, and water.

It does not require electricity or batteries to operate. All one needs to do is pour water into the attached plastic container until full measure. The action of gravity naturally allows water to flow down into the catching pitcher below. The clay pot attached to the plastic container above the pitcher serves as filter.

“As a matter of order, drinking–water should be suitable for consumption, washing/showering and domestic food preparation,” said Dr. Basilia.

Piped in drinking water is the usual source of potable/clean drinking water. However, drinking water may also be obtained from non-piped sources like springs and community wells.

“The control of contamination of drinking-water systems and sources by human feces or fecal contamination where it occurs is very important,” Dr. Basilia stressed.

Tests conducted on water filtered via the ceramic water filter showed a heterotrophic plate count of less than 30, while coliform per 100 ml samples yielded negative results and tests for the presence of E. coli per 100 ml samples also yielded negative.

These mean that water filtered using the candle-type ceramic water filter passes the Philippine National Standard for drinking water.

Lastly, at the Chemicals and Energy Division, Dr. Anabelle Briones and her team developed a salt iodization machine.

A continuous screw-type, it can be used by small salt processors and help them comply with the ASIN Law otherwise known as Republic Act 8172, which promotes salt iodization nationwide.

It can also iodize fine or coarse salt and ensure consistent and even distribution of iodine content. The process is sustainable and employs low operating costs. S&T Media

Vital Signs Issue 85 Vol. 4, March 1-31 2016

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