Local plant validated for ovarian, pancreatic cancer treatment

A local plant, 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. CHUKWUMA MUANYA (Assistant Editor)

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.”

Five pancreatic cancer and three ovarian cancer cell lines were tested that exhibited different resistance to the first line chemo-drug gemcitabine (Gem, for pancreatic cancer), and carboplatin (Cp, for ovarian cancer). Chou-Talalay’s method was used to evaluate drug combination.

The results showed that both Rau and Pao extracts induced dose-dependent cytotoxicities in all tested cancer cell lines, despite their inherent resistance to chemo-drugs. IC50 values for Rau were 140-350µg/ml, and 120-350µg/ml for Pao, depending on the cells tested. Normal epithelial cell MRC-5 was much less affected compared to all the tested cancer cells. The differences of cell viabilities between cancer cells and normal cells were statistically significant, indicating possible low toxicity of these extracts.

To test whether the treatments of Rau or Pao could enhance the cells’ sensitivities to chemo-drugs, the researchers combined either Rau or Pao with gemcitabine to treat pancreatic cancer cells, and with carboplatin to treat ovarian cancer cells.

The results showed a left-shift in the dose-response curves of the combination treatments compared to the corresponding curves with either Gem or Cp alone in all tested cancer cells. Combination indices (CIs) were <1, indicating synergistic effects.

Researchers have also demonstrated that Rauvolfia vomitoria has potent antitumor activity and in combination significantly enhances the effect of carboplatin against ovarian cancer.

The researchers evaluated an important but not yet well-understood aspect of the effect of an extract from the root of Rauwolfia vomitoria, enriched with alkaloids and with reserpine removed, in the treatment of ovarian cancer, used alone and in combination with Cp.

The study was published in the journal Current Therapeutic Research.

Until now, tumour resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer.

In an effort to enhance the effectiveness of platinum-based drugs, the researchers investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with Cp.

The results showed Rau decreased cell growth in all three tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar and combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87 per cent to 90 per cent and ascites volume by 89 per cent to 97 per cent.

Another study published in North American Journal of Medical Sciences showed how Vitamin E supplementation with Rauwolfia vomitoria root bark extract improves hematological indices.

The researchers from Akwa Ibom State University, Uyo, concluded: “We observed that extract of Rauwolfia vomitoria root bark is a useful medication in the treatment of many diseases and the combination of this herbal extract with vitamin E may be of more biochemical and therapeutic significance since the antioxidant vitamin is capable of de-potentiating the adverse effect of this herb.

“Rauwolfia vomitoria with or without vitamin E improved the immunity and enhances the haematological indices of the experimental animals…”

Also, United States researchers from the Columbia University Medical Center, New York, have discovered the potential anti-prostate cancer activity of Rauwolfia vomitoria extract on the growth and survival of the human LNCaP prostate cancer cell line.

The study titled: “Anti-prostate cancer activity of a ß-carboline alkaloid enriched extract from Rauwolfia vomitoria” was published in the International Journal of Oncology.

Meanwhile, a combination of Rauwolfia vomitoria and Citrus aurantium (lime) has received a European Patent for treating diabetes.

Yet another study published in North American Journal of Medical Sciences concluded: “Chlorpromazine (antipsychotic drug) at moderate to high doses (2.0 and 4.0 mg/kg, i.p.), increasing pain perception (hyperalgesic effect) whereas the crude aqueous root bark extract of Rauwolfia vomitoria dose-dependently decreased pain perception (analgesic effect). Reserpine similarly produced an analgesic effect in the mice.

“Chlorpromazine at moderate to high doses (2.0 and 4.0 mg/kg, i.p.) caused an impairment in social behaviour, thus inducing social loss in the mice (implying possible exacerbated depression and social withdrawal in psychotic conditions). The root bark extract of R. vomitoria, however, did not affect social behaviour. On the contrary, reserpine (0.1, 0.4 and 1.6 mg/kg, i.p.) caused a dose-dependent impairment in social behaviour, as seen in poor nest building, hence social loss.

“The same doses of chlorpromazine which produced a hyperalgesic effect induced social loss, consistent with earlier studies on relationship between social behaviour and pain. If this is applicable in humans, chlorpromazine may not be a very good antipsychotic even when it is the foremost and cheapest antipsychotic drug. Whole root bark extract of Rawolfia vomitoria therefore has a great potential as an antipsychotic because its effect is not due to the presence of reserpine alone.”

Hyperalgesia is a condition where a person develops an increased sensitivity to pain.

The study is titled “Comparative effects of Rauwolfia vomitoria and chlorpromazine on social behaviour and pain.”

Chlorpromazine (CPZ) is a first generation commonly used and readily available standard antipsychotic drug listed as one of the most essential drugs by the World Health Organisation (WHO) in 2003. Although chlorpromazine has been used to treat both acute and chronic psychoses it has been associated with side effects such as anti-dopaminergic extrapyramidal syndromes, dry mouth, blurred vision and urinary retention (anticholinergic), neuroleptic dysphoria, blood pressure disturbances, temperature and muscle control (neuroleptic malignant syndrome), diminished libido, erectile impotence and ejaculation inhibition in male patients.