Anti-HIV Activity of Medicinal Herbs: Usage and Potential Development

American Journal of Chinese Medicine,  Wntr, 2001  by Ji An Wu,  Anoja S. Attele,  Liu Zhang,  Chun-Su Yuan

• E-mail
• Print
• Link

(Accepted for publication June 5, 2000)

Abstract: The acquired immunodeficiency syndrome (AIDS) is a result of human immunodeficiency virus (HIV) infection which subsequently leads to significant suppression of immune functions. AIDS is a significant threat to the health of mankind, and the search for effective therapies to treat AIDS is of paramount importance. Several chemical anti-HIV agents have been developed. However, besides the high cost, there are adverse effects and limitations associated with using chemotherapy for the treatment of HIV infection. Thus, herbal medicines have frequently been used as an alternative medical therapy by HIV positive individuals and AIDS patients. The aim of this review is to summarize research findings for herbal medicines, which are endowed with the ability to inhibit HIV. In this article, we will emphasize a Chinese herbal medicine, Scutellaria baicalensis Georgi and its identified components (i.e., baicalein and baicalin), which have been shown to inhibit infectivity and replication of HIV. Potential development of anti-AIDS compounds using molecular modeling methods will also be discussed.

The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is an unprecedented threat to nations as well as to global health (Fauci et al., 1985; Fauci and Artlett, 1998). It is estimated that each year HIV infects at least 2 million people in the United States and more than 10 million people worldwide. Thus, the search for effective therapies to treat AIDS is urgently needed. In order to combat HIV, a colossal amount of money and manpower have been dedicated to searching for compounds that can be developed as therapeutic agents. In the last two decades, several chemical anti-HIV agents have been developed. However, herbal medicines have also been used frequently by HIV positive individuals and AIDS patients as an alternative medical therapy (Kassler et al., 1991).

Conventional Chemotherapy for HIV Infection

According to De Clercq the replicative cycle of HIV is comprised of ten steps that may be adequate targets for chemotherapeutical intervention (De Clercq, 1995a; De Clercq, 1995b). Most of the substances that have been identified as anti-HIV agents can be assigned to one of these ten classes of HIV inhibitors based on the stage at which they interfere with the HIV replicative cycle. These ten steps are: (1) Viral adsorption to the cell membrane, (2) Fusion between the viral envelope and the cell membrane, (3) Uncoating of the viral nucleocapsid, (4) Reverse transcription of the viral RNA to proviral DNA, (5) Integration of the proviral DNA to the cellular genome, (6) DNA replication, (7) Transcription of the proviral DNA to RNA, (8) Translation of the viral precursor mRNA to mature mRNA, (9) Maturation of the viral precursor proteins by proteolysis, myristoylation, and glycosylation and (10) Budding, virion assembly and release. Step 4, a key step in the replicative cycle of retroviruses, which makes it distinct from the replicative cycle of other viruses, is the reverse transcription catalyzed by reverse transcriptase. Another target for therapeutic intervention is step 9, particularly the proteolysis of precursor proteins by HIV protease. The majority of chemotherapeutic strategies have, therefore, focused on the development of retroviral enzyme inhibitors.

The U.S. Food and Drug Administration (FDA) has approved a number of anti-HIV drugs for clinical use (De Clercq, 1999). However, these medications have limitations such as high cost, peripheral neuropathy and decreased sensitivity due to the rapid emergence of drug resistant mutant virus strains, and adverse effects like bone marrow suppression, and anemia (Lee and Morris-Natschke, 1999; Vandamme et al., 1998). Thus, more effective and less toxic anti-HIV agents are still needed. In addition, alternative approaches, including herbal therapies, long-term screening of plant extracts, particularly anti-infective or immunomodulating medicinal herbs, and the structural modification of lead compounds, have been attempted.

Studies of Medicinal Herbs on HIV Infection

Use of Herbs in Asia and North America

Herbal medicine has been used in China for centuries. Even after opening its doors to western medicine two centuries ago, China still relies heavily on traditional medicine and herbal therapies because of their efficacy. Indeed, the recent focus of the Chinese government has been to propel research at its institutes and universities towards developing efficacious herbal drugs, particularly as anti-cancer, anti-cardiovascular disease, and immunomodulating agents (Huang, 1999).

In China, medicinal herbs are being used in the treatment of HIV positive subjects and AIDS patients. One example is the traditional Chinese medicinal herb Tian-Hua-Fen (Trichosanthes kirilowii), which appears in the classical Chinese medical reference work Compendium of Materia Medica from the late 14th century. Tian-Hua-Fen has been used in China for hundreds of years to reset menstruation and expel retained placentas. Trichosanthin (TCS), an active protein component isolated from Tian-Hua-Fen, has been shown to inhibit HIV infection and has been used in the clinical treatment of AIDS (Zhao et al., 1999).