New Perspectives on Aloe New Perspectives on Aloe Young In Park Seung Ki Lee Editors With 85 Figures, Including 16 Color Plates Young In Park Seung Ki Lee Korea University Seoul National University Seoul, Korea Seoul, Korea Preface The CAP project for comprehensive aloe research was launched in June 1993 and completed its first stage in 2001. I am deeply moved by this publication con- taining eight years’ research outcome on aloe. Before launching the CAP project, some members of the CAP research team did not know the real nature of aloe, or simply recognized it as a “functional health food or a dietary supplements” that is used as more of a panacea. In January 1993, I was invited to visit Aloecorp, an America-based local corporation and aloe plantation located in Harlingen, Texas and Tampico, Mexico. Together with several members of CAP research, I took part in that journey, and all of us were very impressed with the aloe industry. In particular, the seminar organized by American aloe researchers was so impressive it led us to have special interest in aloe. In retrospect, we maintained continuous discussions on aloe around the clock. We felt that we became very enthusiastic about aloe, ended up calling our- selves “crazy aloe people” (CAP). Thus, our project was named the “CAP Project” and it was the beginning of the new Creation of Aloe Pharmaceuticals (CAP). The CAP project was commenced in June after the visit, and since its begin- ning, we organized a systematic research team to pursue aloe research. Dr. Seung Ki Lee, a professor at Seoul National University, and twelve other professors from various universities in Korea joined the team. An additional twenty-six professors from prominent universities and their staff have participated in the project. Many active ingredients from natural aloe have been isolated and analyzed. These conclude that aloe is medically effective in the following cases: promoting liver cell growth, angiogenesis, growth of epithelial cells, anti-allergic effect, skin whitening effect, and protective effect on nephrotoxicity. These results became the groundwork for the development of functional health foods and cosmetics. Especially, the “development of tolyl-based skin whitening agent” project was proven scientifically reliant, as it was adopted as one of the G7 projects by the Ministry of Science and Technology in Korea. In addition, the “Raman whitening product,” which was produced on the basis of the project, was awarded the “IR52 Jang Young-Shil” prize by the Korea Industrial Technology Association and Maeil Economy Newspaper contest in 1998. It was the first case that a cosmetics corporation received an award in the industry. In addition, a study on utilizing an anti-allergic substance, Alprogen, was also adopted as one of the G7 projects and continued for five years. “Development of Prokidin as a protective agent against Cispatin induced nephrotoxicity” was also selected as one of core projects by the Ministry of Health and Welfare. All of these R&D efforts resulted in seven domestic patents and several international pending patents. vi Preface After the completion of the first stage of the CAP project, Stage 2 was launched in 2002. The second project focused on reviewing less sufficient tasks of the first project and was more in-depth, aiming to discover new functions of aloe using more advanced methods of verifying aloe’s efficacy. It can be said that the remarkable performance during the past thirteen-year study on aloe is unimaginable, compared to where we were when we initially launched the project. Our systematically designed project has been pursued by a top-down approach and now evaluated to operate in a systematic and efficient way. I think it is a model of a successful R&D project. I sincerely would like to give special thanks to Professor Seung Ki Lee and other participating researchers who had worked day and night for this project. I would also like to extend my appreciation to the officers and employees of the Namyang Aloe Company that provided much-needed assistance in times of diffi- culty. Park, Young In, Ph.D. Editor in Chief Chairman, The CAP Research and P lanning Committee Young In Park, Ph .D. Korea University, Seoul, Korea Seung Ki Lee Seoul National University, Seoul, Korea Contents Preface ……………………………………………………………………v Contributors………………………………………………………………ix 1. Overview of Aloe study………………………………………………………..1 2. The history of Aloe……………………………………………………………..7 3. Chemical components of Aloe and its analysis………………………………19 3.1 An epitome of chemical components and low molecular compounds…….19 3.2 Proteins in Aloe……………………………………………………………35 3.3 Carbohydrates……………………………………………………………57 4. Efficacy of Aloe……………………………………………………………….63 4.1 Wound healing effect………………………………………………………63 4.2 Angiogenic effect………………………………………………………82 4.3 Anti-allergic responses …………………….………………………………95 4.4 Skin whitening effect……………………………………………………127 4.5 Cell growth-stimulating effect……………………………………………136 4.6 Protective effect on nephrotoxicity………………………………………143 4.7 Immunomodulatory activity………………………………………………155 5. Quality control and standardization of Aloe products .……………………...169 6. Perspective of industrial application of Aloe vera…………………………...191 Contributors Chung, Myung Hee, Ph.D. College of Medicine, Seoul National University 28 Yeonkun-Dong, Jongno-Ku, Seoul 110-460, Korea Choung, Se Young, Ph.D. College of Pharmacy, Kyung Hee University 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea Jo, Tae Hyung Unigen, INC. 200-1, Songjung-Ri, Byeongcheon-Myeon, Cheonan-Si, Chungnam 330-863, Korea Kim, Kyeong Ho, Ph.D. College of Pharmacy, Kangwon National University Chuncheon 200-701, Korea Kim, Kyu Won, Ph.D. College of Pharmacy, Seoul National University 599 Kwanak-ro, Kwanak-gu, Seoul 151-742, Korea Kim, Young Shik, Ph.D. Natural Products Research Institute College of Pharmacy, Seoul National University 28 Yeonkun-Dong, Jongno-Ku, Seoul 110-460, Korea Lee, Chong Kil, Ph.D. College of Pharmacy, Chungbuk National University 48 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea Lee, Seung Ki, Ph.D. College of Pharmacy, Seoul National University 599 Kwanak-ro,Kwanak-gu, Seoul 151-742, Korea Park, Jeong Hill, Ph.D. College of Pharmacy, Seoul National University 599 Kwanak-ro, Kwanak-gu, Seoul 151-742, Korea Park, Young In, Ph.D. School of Life Sciences and Biotechnology, Korea University Anam-dong, Sungbuk-gu, Seoul 136-701, Korea x Contributors Son, Byeng Wha, Ph.D. Department of Chemistry, Pukyong National University 599-1 Daeyeon 3-d ong, Nam-gu, Busan 608-737, Korea Sung, Chung Ki, Ph.D. College of Pharmacy, Chonnam National University 300 Yongbong-dong,Buk-gu, Gwangju 500-757, Korea Ro, Jai Youl, Ph.D. Department of Pharmacology, Sungkyunkwan University School of Medicine Cheoncheon-Dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Korea 1. Overview of Aloe study Lee, Seung Ki, Ph.D. College of Pharmacy, Seoul National University 1.1. Research background 1.1.1. Historic background of Aloe as folk medicine Aloe belongs to Liliaceae, the family of perennial tropical plants of African ori- gin. More than 360 species are known worldwide. Species of aloe which have been used as folk medicine include: Curacao Aloe (Aloe barbadensis or Aloe vera), Cape Aloe (Aloe ferox), and Socotra Aloe (Aloe perryi). Records of the use of Aloe vera as folk medicine date to antiquity with an early account from around 1500 B.C. being described in Sumerian Clay Tablets and the papyrus Ebers, stored in Leipzig University. However, the earliest known record of the folk use of aloe is an engraving in an Egyptian temple, which mentions aloe as the sanctuary plant of immortality that is dated to 4000 B.C. Ancient records in Egypt, Rome, Greece, Arabia, India and China also demon- strate the use of aloe both as a medicine and cosmetic compound. According to these records, Aristotle persuaded the king Alexander to conquer Socotra Island, located off the east coast of Africa, in order to acquire aloe for use in healing the wounds of soldiers. It is also written that Cleopatra used aloe gel to maintain her beauty. This demonstrates that Aloe has been used as medicine and a cosmetic compound from the earliest recorded history. The first somewhat detailed description of the pharmacological effects of aloe is recorded in “The Greek Herbal”, written by Dioscorides in the first century AD. According to such literature, Aloe has multiple pharmacological effects on healing wounds, burns and frostbite, constipation, insomnia, stomach disease, pain, hem- orrhoids, itching, headache, hair loss, gum disease, kidney disease, blisters, sun- burn and more. 1.1.2. Scientific approach of Aloe research and the current status Once a multipurpose folk medicine, the use of aloe has been dramatically re- duced with the rise of the pharmaceutical industry in Western Europe. Due to the fact that the tropical plant could not be cultivated in Western Europe, it joined the ranks of many such plants which were classified as “folk medicine” or “botani- cals”. The decline in the popularity of aloe can be traced by counting published re- search articles related to it. The majority of recently published scientific studies of aloe are concerned with the classification of the plant itself or its components.