Herbal remedies rot at Kemri shelves as financial constraints keep them from pharmacies

You will either find them in the laboratory or in the deep of the Ngong Forest in Nairobi, or even on private farms collecting herbs. But more than 30 years after the Centre for Traditional Medicine and Drug Research was established, their products are still not on the market.

However, the work the 16 researchers at the division of the Kenya Medical Research Institute have done over the years lines the pages of scientific journals such as the Journal of Complementary and Alternative Medical Research.

The researchers’ work is cut out for them – their mission is to improve the quality of human health and life by providing scientific evidence on the quality and safety of traditional medicines – and they have not disappointed: They have studied nearly 20 medicinal plants with potential for treating ailments such as malaria, asthma and cancer and managing diabetes. They have also developed anti-viral compounds and immune moderators.

Yet not many Kenyans, including two out of three people who rely on herbal medicines for their primary healthcare needs, are aware that there are well-researched and clinically proven traditional medicines, that can hold their own when put side by side with conventional medicines.

For one to get to know the shelf life of a product, it has to be tested often every six months.

NO FUNDS

“We still have not gotten to this stage since we don’t have the funds to enable us to take it to the laboratory to confirm the viability,” Dr Mwitari.

Starting out as a centre to authenticate and conduct safety studies and research the mechanisms of herbal remedies, the centre has evaluated the medicinal properties and side effects of compounds derived from plants, with a view to isolating compounds for the control and management of infectious, parasitic and non-communicable diseases.

Thereafter, the centre moved from simply authenticating to innovation, which resulted in medicinal products. Thanks to the work of the researchers, medicines for malaria, asthma and hypertension have reached the pilot stage.

An anti-viral that works against herpes has even been registered by the Pharmacy and Poisons Board, but you won’t find it, or any of the other remedies, on pharmacy shelves. According to the director of the Centre for Traditional Medicine and Drug Research Peter Mwitari, the reason for this is financial constraints.

Developing a drug from scratch takes 15 years on average, from proposal to pilot product, and that costs a pretty penny. For instance, the centre submitted three funding proposals to the Ministry of Health, which required Sh14 million. However, they only received Sh3.9 million for various uses, which include ensuring that conventional drugs meet quality standards.

As Dr Mwitari explains, it costs millions to develop, test and patent a product, and renewing the patent every year would cost money, which is not available. Moreover, the centre needs better equipment to conduct research that will yield the right products.

“We write a proposal with specified objectives and once the pilot product is out, the funding ends. We rely on the government for funding to carry out research, but it is not enough. We need partners to help us develop and produce the products for the market,” explained Dr Mwitari.

“We have carried out a lot of research showing that the herbs have the potential ascribed. We need to move to the next stage of products for the health sector. The public needs to enjoy the fruit of the taxes they pay, which fund us,” said Dr Mwitari, adding that there is committee to address the linkage between laboratory and industry and look into the possibility of a private-public partnership to ensure the products get into the market.

In the absence of adequate financial support from government, one would hope that the centre might get research grants, but Dr Mwitari says that it is rare to find donors who will fund routine assessment of traditional medicines.

SCALING

When stacked up against competing research from multinational pharmaceutical companies working on conventional medicines, traditional medicine research can only get breadcrumbs, if anything at all. The little grants the centre receives are not enough to complete the haul.

“After pilot production, for us to scale up to industry is another ball game altogether. Once research is done and a pilot product is out, it ends there,” adds Dr Festus Tolo, another researcher who has been at the centre for nearly 30 years.
Dr Tolo has worked on several products, but his signature remedy is ZEDUPEX, an anti-viral used to treat herpes, and a salt for patients with high blood pressure. The two products took 10 years each to develop.

Closely related to the challenge of funding, which also affects the possibility of the products being taken to clinical trial, is that the laboratories are not well-equipped to undertake serious research. Most of the equipment at the centre is outdated, having been purchased in the ‘80s. Most of the samples are sent outside the country, since there is no nuclear magnetic resonance spectroscopy (NMR) to read the structure when a research is to be conducted.

“If we had an NMR, we would get the structures of the compounds that we are isolating from our medicinal plants. We do not have a machine, so we rely on institutions outside the country to get our structures elucidated. When we send our samples outside the country, it takes long for results to come back,” explained Dr Mwitari, adding that the government would have to equip the labs because donor money cannot be used to buy equipment.

“We need research funds to buy consumables and equip our laboratories. We have sufficiently trained staff, but without the necessary infrastructure we cannot make progress,” he said.

NEW POLICY

However, with the development of the Draft Policy on Traditional Medicine and Medicinal Plants, things might change. A technical working group chaired by Dr Mwitari is looking at the policy, which will be used to regulate traditional medicine and integrate it in the public health system.

The policy will also document the availability of plants and promote nurseries and herb gardens for conservation of medicinal plants and research. It will also tackle equitable sharing of benefits from medicinal plants, as well as enhancing production while ensuring safety and efficacy of products.

The document, which will also serve as a reference point for medical practitioners, regulators and consumers, is expected to be presented to the Cabinet Secretary for Health at the end of the month.

But even as the country moves towards bringing traditional medicine into mainstream healthcare, there are questions on sustainable exploitation of the medicinal plants, whose extinction in the event of overexploitation would jeopardise the very foundations of traditional medicine.

The draft policy aims to address this too, with plans to domesticate some of the wild herbs to ensure continuous supply for large-scale production of remedies, without depleting wild stocks.

Moreover, according to Dr Mwitari, the government should come up with an entity to manufacture the drugs soon after the research is done, just like with conventional medicine.

“We have so many samples that need to be produced, but we do not have the factory,” he said.

HOW IT IS MADE

To begin with, the researcher identifies a disease that needs attention. For instance, cancer has increasingly become a national problem.

Once the problem has been identified, the researcher writes a proposal, for say, an alternative medicine for cancer, derived from plants. This is followed by background research and literature review, to uncover similar research that might have been done elsewhere.

Once that is done and dusted, it is time to look for funding, then identify where to get the raw materials. Herbalists usually come in handy for this, but a qualified botanist must also help identify the plant. Once the plant is identified, it is harvested sustainably and transported to the laboratory.

The raw materials are cut into small pieces, dried at room temperature, then ground into a fine powder using a mill. The powder is heated in various ovens to come up with an extract, that is then taken through biological assessment to measure activity. The extract is also observed to establish whether it is toxic. After that, the researchers use cells grown in the laboratory or mice or primates to test the activity and safety of the compound.

The compound responsible for the activity observed is then identified by name. Then ,the compound is taken through the formulation process to either produce capsules, creams, powders or soaps or a syrup. This is where the pharmacists come in.

After coming up with the formulation, it is taken back through the system to check for safety and activity, followed by establishing dosage. After that a pilot product that can be rolled out in large-scale production is produced, and a patent can be sought. This is followed by clinical trials with humans, but because clinical trials cost more money than available, the products have not been taken through that last stage.

One of the most successful products was ZEDUPEX, which they sold in small scale through the production department. They have not produced in the past three years.

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Medicinal compounds under study at Kemri

1. Carissa edulis roots have shown remarkable activity against herpes simplex virus, including resistant strains.

An extract of a 250mg oral dose used on mice infected with wild-type or resistant strains of HSV delayed the onset of HSV infections by more than 50 per cent.
It also increased the mean survival time of treated infected mice by between 28 and 35 per cent relative to the infected untreated mice. The mortality rate for mice treated with extract was significantly reduced between 70 and 90 per cent as compared with the infected untreated mice that exhibited 100 per cent mortality. No acute toxicity was observed in mice at the oral therapeutic dose of 250 mg/kg.

These results suggest that this herbal extract has potent anti-viral agents against herpes simplex viruses that can be exploited for the development of an alternative remedy for HSV infections since the available drugs are developing resistant strains of HSV.

From these experiments, a powder taken in tea and ZEDUPEX, TMR5 a cream applied to the genitals was developed and licensed by the Pharmacy and Poisons Board in 2015 to treat genital herpes.

2. Cyperus papyrus reed derived from papina reeds from where/found where? Research indicated that the salt derived from the reeds has a favourable potassium to sodium ratio, making it suitable for hypertensive patients for the regulation of high blood pressure.

The herbal salt can also be used to preserve meat and is a source of trace elements such as chromium, zinc and manganese.

Moringa oleifera and Indigofera arrecta leaves have anti-cancer agents and combining plant extracts and derived compounds for use with commonly-used cancer drugs, has shown a marked improvement of the efficacy of the conventional drugs and reduced toxicity (side effects).

The extracts showed anti-proliferative activities against breast cancer, prostate and cervical cancer cell lines. The extracts were not cytotoxic towards Vero cells. The plant extracts synergistically inhibited the growth of cancer cells.

The plant is rich in vitamin A, B, C, D, E and K and has been employed in the treatment of many diseases traditionally such as hysteria, scurvy, prostate problems and bladder discomfort.

It also has a wide array of medicinal properties including anti-inflammatory, antioxidant, strengthening of the immune system and wound healing.

Moringa seeds are effective against skin-infectious bacteria while the roots and bark are used to relieve cardiac and circulatory problems. The leaves have high iron content thus used in anaemia treatment.

Indigofera arrecta leaves are traditionally used in the treatment of epilepsy, nervous disorder, ulcers and diabetes mellitus. The leaves also contain antibacterial activities with the potential to heal sores. However, their anticancer activity needs to be investigated further.

This study tested the antiproliferative activity of the plant's extracts against selected cancerous and normal cells. The study further evaluated the synergistic effects of extracts from the two plants with 5-Fluorouracil, an antimetabolite and anti-cancer chemotherapeutic drug that is widely used in the treatment of colon, prostate, breast cancer.

A number of side effects have been observed in the usage of the drug alone including hair loss, nausea and vomiting, loss of appetite and diarrhea but when it was given with a combination of the two extracts, no side effects were observed.

3. Withania somnifera as an immune modulator for cancer and diabetic patients.

A study published in the European Journal of Medicinal Plants, evaluated and demonstrated the antiproliferative activity of plant extracts against breast and prostate cancer cells.

The selectivity indices demonstrating both toxic and selective potential of the different plant part extracts. This, attributed to the different phytochemical composition and concentration in the leaves, stem and roots.

4. Tragia brevipes and Tetradenia riparia have been widely used.T. brevipes relief stomach pain and in the treatment of rheumatism while T. riparia; heal chest pains, stomachache, malaria and act as an antioxidant.

However, Kemri is investigating their potential anticancer activity. The total phenolic content was determined and anti-proliferative activity of the Methanol-Dichloromethane extract from the leaves evaluated against cancerous cell lines.

Methanol-Dichloromethane extracts from the two exert anti-proliferative activity on breast, cervical and prostate cancer cells.

Their leaves could be probable candidates in cancer treatment and management. The plants extract depicted low toxicity to normal cells as shown by high selectivity index values.

5. Prunus Africana widely used as an anti-allergy while Kemri researchers are investigating it for treating prostate cancer.

6. Capparis tomentosa (African caper or woolly caper bush) is a plant that grows in stressful environments like hills or mountainous areas and entwines.

The plant can treat high blood pressure, asthma, allergy, nerve problems, depression, fibroids, infertility and skin diseases but the centre is conducting a research to investigate if it can treat cancer.