Ecballium elaterium: Part 1: Botanical and Biological Characteristics Relevant to the Management of Hepatitis C and Other Diseases

Stephen Holt MD*, Said Shalaby MD**, Essam Hob Allah PhD**, *Distinguished Professor of Medicine, **National Research Centre, Cairo, Egypt.

Introduction

Derivatives or components of Ecballium elaterium (A. Richard, “Squirting” or “Jumping” Cucumber, family Curcurbitacea) have been used as a natural medicine in Mediterranean and African countries for centuries. The described actions of this herb include: antihepatotoxicity , the prevention of hepatitis induced liver cirrhosis and the treatment of jaundice in rats or humans , , the effective management of sinusitis or nasal obstruction and reversal of tissue edema in mice .
The crude juice of Ecballium elaterium (Ee) has been used most often in herbal medicinal practice, but it is often toxic. Reports of variable toxicity exist with crude concentrates of Ee, including: has included antifertility effects in female mice , cytotoxicity , , and occasional deaths from poisoning. In contrast, water-distilled fractions of Ee juice given at approximate homeopathic dilutions 1x (LD times) are considered safe with retention of efficacy for several designated uses (vide infra). Ecballium elaterium has been widely used as a treatment for Hepatitis C (viral infection (HCV) in Egypt.

This use of Ee in treating liver disease is deeply rooted in Egyptian folklore medicine. The interest in Ee has been reactivated largely as a consequence of the emerging epidemic of Hepatitis C virus infection (HCV) in Middle Eastern countries, especially Egypt . Hepatitis C virus infection produces an indolent disease or diathesis that accounts for a large proportion of all patients with chronic liver disease. Hepatitis C is anticipated to cause major global increases in morbidity and mortality in the future .

Current treatments for HCV possess major disadvantages and limitations . While pegylated interferon alpha combined with ribavirin are preferred treatments for HCV, these interventions are expensive, difficult to tolerate and limited in safety and effectiveness. Interferon/ribavirin treatments have unpredictable outcomes13 in patients with HCV.

Hepatitis C virus infection is a recalcitrant disorder that afflicts tens of millions of individuals worldwide . The emergence of HCV in third world countries cannot be impacted readily by expensive, high-technology approaches, such as those that utilize interferon and antiviral drugs (ribavirin). These treatments require skilled administration and extensive monitoring. In addition, these management strategies are not portable and they are often prohibitively expensive. Any alternative, low cost intervention for HCV, with even partial effects on the clinical course of HCV, would represent a major breakthrough in therapeutics. This article describes the ethnobotanical discovery of derivatives of Ee as a potentially-viable, natural “treatment” for HCV and other disorders.

HCV: A Brief Overview

Infection with the Hepatitis C virus (HCV) is more common than HIV (Human Immune Deficiency Virus) infection, but chronic Hepatitis C receives much less overall attention than AIDS (Acquired Immuno-deficiency Syndrome). Hepatitis C virus infection is a major threat to humankind, with gargantuan medical and economic costs. The virus was recognized in clinical practice in 1975, with its distinction from Hepatitis A or B virus infection. It was labeled initially as non-A, non-B hepatitis11. The viral organism causing non-A, non-B hepatitis was indentified in 1989 by Michael Houghton and his colleagues. The serological diagnosis of HCV was discovered in 1990, followed by subsequent refinements with direct measurements of the presence of viral particles.

Early antibody tests to diagnose HCV have been replaced by measurements of viral load using a polymerase chain reaction (PCR). These measures of the presence of HCV have been further refined by transcription mediated amplification (TMA) technologies. The Hepatitis C virus has a variable genetic structure, resulting in six principal genotypes. These viral types are classified by numbers 1 through 6 and many viral subtypes exist (e.g. 1b, 2b, etc.). In the US, the most common genotype is type 1 occurring in about 75% of all presenting cases of HCV. In contrast, the genotype in Egypt, where HCV is very common, is most often type 4. Studies of blood donors in Egypt show a prevalence of HCV in about one in five individuals (20%). Genotyping of the virus is believed to have value in predicting the severity of disease and clinical responses to interferon/ribavirin treatments13.

Hepatitis C virus infection produces chronic debilitation. Chronic Hepatitis C is of variable severity and progression to cirrhosis and liver decompensation. Its clinical course may wax and wane for years. About 10,000 deaths occur annually in the US as a result of HCV; and it is the most common reason for liver transplantation. Arguments prevail about the routes of transmission of HCV but transfer of blood or tissue fluids clearly operate. Oral-fecal routes, intrauterine and sexual transmissions of HCV may arguably occur.

The usual and customary treatment of HCV, comprising pegylated interferon alpha and ribavirin, may sometimes reduce HCV morbidity and mortality. The adverse effect profile of this “standard, interferon/ribavirin treatment” is onerous, with the development of fatigue or flu-like symptoms in 60% of treated cases. Other common adverse events include: depression (30%), neutropenia (20%) and anemia (20%), approximately. So pernicious are these side effects of interferon/ribavirin administration, that they result in discontinuation of treatment in more than one in five cases, in spite of the stringent selection criteria that are needed to administer the therapy, in clinical trials or practice13.

Some arguments support the notion that the “standard treatment of Hepatitis C viral infection may on occasion be worse than the disease”. Contraindications to therapy with interferon/ribavirin are many, including: hemoglobin less than 13g/dl in men or less than 12g/dl in women, neutrophil count less than 1∙5 k/micro ml, platelet count less than 75 k/micro m and a blood creatinine greater than 1∙5 mg/dl.

Other relative or absolute contraindications to standard interferon treatments include: cirrhosis of the liver, decompensated liver disease, depression, diabetes mellitus, social instability or illicit drug use. African-American individuals with HCV seem to have a poorer clinical outcome with standard HCV treatments, compared with other ethnic groups. A good treatment outcome in the conventional management (interferon/ribavirin) of HCV is often reported as a sustained viral response (SVR), but the cost of this outcome in terms of morbidity caused by the therapy is not clear in routine medical practice13. In brief, the disadvantages and limitations of interferon/ribavirin treatments appear very challenging for doctors and patients. The circumstances have prompted the call for effective, simpler treatments for HCV.

Ecballium elaterium (Ee): A Brief Overview

Ecballium elaterium is a perennial, squash-like vine with a trailing stem (Figure 1). The plant is a bristly, tendril-bearing succulent. The leaves of the plant are chordate with long, lobed, hispid, pale-green morphology. The flowers of Ecballium elaterium are a pale yellow and the fruit of Ecballium elaterium is oblong, broad and pale green with fleshy prickles. Inside the fruit is mucilaginous juice, containing abundant pale-brown seeds. The origin of the Latin name of the plant, “Ecballium”, has a Greek derivation where “ek” means “to throw”, referring to the fruits ability to expel its contents when it is ripe. Hence the name “Squirting Cucumber.”

At first sight, the described toxicity profile of Ee in early literature seems to disqualify this plant from any perception that it could be used as a safe remedy of natural origin. Present research (Holt S, Shalaby S, Hoballah E) demonstrates that a water, distillation extract (a tea) of Ee is not only safe in controlled, animal and human observations, but it may be a viable approach to the cost-effective, portable, nutritional management of HCV , , (vide infra).

It is useful to discuss the development of Ee as a remedy of natural origin by reference to its evolution in the science of pharmacognosy. While Ecballium elaterium in whole or certain “crude forms” (juice) has demonstrable toxicity, it must be emphasized that in proprietary, water-extracted forms it appears to be a simple, gentle, antiviral agent, with potent and versatile treatment properties in HCV and other disorders.

Elaterium BP, Elaterium, Elaterinum BP and Elaterin (Pulvis elaterini Compositus BP and Trituratio Elaterini USP) appear prominently in the British Pharmaceutical Codex (1911). This codex was published by the direction of the Council of the Pharmaceutical Society of Great Britain . In addition, Ecballium is reviewed in the Manual of Materia Medica and Pharmacology that comprise organic drugs which were recognized by the United States Pharmacopoeia (1927) . In the British literature, it is clear that medical scholars in Edinburgh and Manchester were among the first to describe the clinical effects of Ee used in crude and toxic concoctions (Pharmacopoeia used in Manchester Hospitals, interpreted by Craig Thornber) .

Early descriptions of the therapeutic use of crude extracts of Ee, describe this botanical as an energetic hydragogue that worked “with great violence in doses of a few grains”. The early concoctions of Ee caused diffuse inflammation of the tubular digestive tract, characterized by vomiting, griping and profuse diarrhea18. Its use was recommended in the “plethoric states” of pulmonary edema, ascites, cerebral affections, narcotic poisoning, dropsy with liver or heart complications and chronic inflammation of the bladder18, sometimes in an ‘ill-advised manner.’ The early US literature19 discussed indications for its use similar to those proposed in Britain18, with comments about its medical applications falling into disfavor, quite predictably.

Against this somewhat scary toxicological background of the early documented use of crude preparations of Ee, a renaissance interest in the biopharmaceutical potential of components of Ee has blossomed in recent years , , , , , , , , , . Much interest has focused on the contents of curcurbitacins in Ee. Lavie and Glotter (1971) proposed many medicinal properties of the triterpine (curcurbitacin) contents of several plants. Attention has been drawn to the cytoxtoxic and anticancer action of these compounds , , , together with their actions on increasing capillary permeability31 and anti-inflammatory or anti-viral effect , . The constituents of Ee have been examined in many publications, using a variety of analytic techniques , Chromatographic separation of derivative residues of Ee show the presence of curcubitacins (D, E and I) with mixed phenolic compounds, novel lignans, mixed polysaccharides and essential nutrients38.

While much of the described analytic work on Ee is of great interest in pharmacognosy, the presence of highly bio-active and potentially toxic substances in Ee led the authors to seek a safe, simple water extract of Ee. The rationale for producing this extract was based on the observations made in folklore medicine in Egypt, where “tea” or distilled preparations of Ee have not been found to cause the unpleasant effects that are sometimes experienced with the ingestion of crude juice of Ee.

The proprietary technique for the preparation of a distilled water extract of Ee has resulted in the development of a safe, dietary supplement which has been shown to support liver structure and function, with in-vitro and in-vivo evidence of anti-viral actions. The remainder of this discussion will focus upon the recently developed water extract of the fruit of Ecballium elaterium , , . This water extract of Ee has been shown to be safe and well tolerated in many individuals, under medical supervision (vide infra).

The Water Soluble Fraction of Ee

The development of the water soluble fraction (tea) of Ee was prompted by the long-standing folklore or ethnobotanical applications of Ee. Rural village people in Egypt have reported their anecdotal success in the treatment of themselves or relatives with Ee “tea” or “juice” made from the fruit of the plant. These benefits have been reported in a frequent but anecdotal manner by laypersons in circumstances of presumed HCV infections, influenza and chronic sinusitis.

The study of the biological or biopharmaceutical potential of medicinal plants has become of major research interest in recent times. This interest has blossomed6/6/2008 as the limitations of drug-modeling or synthetic chemistry becomes increasingly apparent in the treatment of many diseases, e.g. chronic viral disease. The obvious challenge in pharmacognosy is to isolate and identify the active components of medicinal plants, as a pathway to provide an evidence-base for disease treatment. While this pathway has most often been used in drug development, it is used increasingly to provide a greater evidence-base for the use of nutraceuticals, natural medicines, alternative treatments, herbal remedies or simple dietary supplements.

In brief, my colleagues and I have examined the contents of water-distilled fractions of Ee by high performance liquid chromatography (HPLC) and gas chromatography combined with mass spectrometry (GCMS), in collaboration with colleagues at the Egyptian Research Council and the University of Cairo, Egypt. On HPLC three distinct peaks are visible in the water extract of Ee. These chromatographic peaks appear to be quite stable for more than two years in replicate measurements. The use of GCMS has confirmed the observations on HPLC and resulted in identification of…

Sources of Ecballium

Ecballium elaterium is most often described as a Mediterranean plant but it can survive harsh environmental conditions. The scientific work described in Part II of this two part article has been performed using water-distilled extracts of Ee which grows in the Middle East, notably the Sinai desert region, Northern or Southern Egypt, Jordan and Libya. The habitat of Ee has been described as Western Asia, North Africa and the Mediterranean basin, where it is found in dry, waste places. However, Ee is known to grow in Northern European countries (Britain), the United States and Indonesia. Whether or not types of Ee grown in different locations have the same biological actions as Ee from Middle Eastern countries remains unclear. Therefore, the precedent created by the present work can only applied to Ee that grows in Middle Eastern countries, in the vicinity of Egypt.

Elegant studies on the habitat in which wild stocks of Ee grow show this plant to be quite hardy . In brief, Ee can grow on calcareous soils that are free of saline or of low salinity, with a high pH (8.08 – 8.65) and a highly variable content of organic matter42. The ubiquitous occurrence of Ee supports the conclusion that this plant is not readily endangered and it can be used as a sustainable supply of medicinals, even from wild-crafted sources.

Conclusion

Part 1 of this two part article has defined the biological and botanical characteristics of Ee as a premonitory discussion of its uses in natural medical treatments. The potential treatment applications of Ee are discussed in Part 2, or this two part series of articles, with special reference to its effects in humans with HCV infection.

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