Hieronder treft u een brief aan, geschreven door een board-certified internist,
Dr. Les Berenson MD FACP, welke wij met zijn instemming hier publiceren.

Vervolgens een heel uitgebreid document met wetenschappelijke informatie.

Dr. Berenson is een van de vele artsen die met een mangosteendrank werken,
zo ook The World Renowned Cancer Surgeon Amod Tootla, M.D., F.A.C.S., F.I.C.S.
Dr Tootla's licensed to practice in 20 different countries & has the distinction of having introduced robotic surgery in the United States.
He's a pioneer of laparoscopic colon surgery and has published numerous papers in the most prestigious medical journals of the world.

Dr Tootla has currently over 1,000 of his patients taking Mangosteen juice

Mocht u als arts intercollegiaal overleg met uw collega in de VS
willen neem dan contact met ons op, zodat wij daarin kunnen bemiddelen.

Brief van:
Les Berenson MD, FACP  Seattle, Washington

Natuurlijke genezing uit een fles.

De afgelopen 25 jaar van mijn carrière in Interne Geneeskunde waren volledig gericht op het voorkomen van ziekten en het verbeteren van de gezondheid op een natuurlijke manier.
Ik heb gedurende mijn hele carrière voeding en de invloed ervan op ons lichaam bestudeerd.
Ik vond het geweldig om patiënten te helpen het heft in eigen hand te nemen en hun levensstijl te veranderen. Velen konden, doordat ze gezonder werden, stoppen met hun medicatie.

Toen ik over mangosteen hoorde, was ik heel erg sceptisch maar toch wel open minded. Sceptisch zijn zonder open te staan om het te onderzoeken, hebben er in het verleden voor gezorgd dat ik teveel goede dingen was misgelopen.
Hoe was het mogelijk dat een vrucht zo'n diepgaande impact had en zoveel veranderingen op cellulair niveau in het lichaam kon bewerkstelligen? Omdat ik zo verschrikkelijk sceptisch, maar toch ook nieuwsgierig was, besloot ik het grondig te onderzoeken.

Ik ontdekte dat de Mangosteen vrucht al honderden jaren werd gebruikt in de traditionele volksgeneeskunde. Ongeveer een eeuw geleden zijn wetenschappers begonnen met het onderzoeken van de vrucht om te zien of er bewijs was dat de werking ondersteunde.
Een nieuw type anti-oxidant werd ontdekt: Xanthonen. Er zijn in de natuur 200 xanthonen te vinden, de mangosteen vrucht bevat er meer dan 40! Sommigen hebben ontstekingsremmende eigenschappen,  anderen anti-tumor, anti-diabetis, sommigen met eigenschappen om de ziekte van Alzheimer tegen te gaan en sommigen met eigenschappen om infectieziekten te bestrijden.
Wat de Mangosteen vrucht uniek maakt is de synergie van de 40 anti-oxidanten die samenwerken in het lichaam en vooral de natuurlijke ontstekingsremmende eigenschappen.

23 Februari 2004 stond er een speciaal artikel in Times Magzine over "De Stille Moordenaar" dat het verband uitlegde tussen chronische ontsteking in relatie tot Alzheimers, hartziekten, kanker, diabetes, reuma, artritis, lupus, auto-immuun ziektes, MS, astma, allergieen en andere ziekten. Mangosteen juice is een van de weinige supplementen die deze ontstekingsremmende eigenschappen bevat!

Vervolgens stuitte ik op ruim 300 persoonlijke ervaringen. Elke arts behandelt zijn patiënten door ze te onderzoeken en te luisteren naar wat ze ervaren. Artsen doen geen dubbelblind onderzoek met hun patiënten. Ze behandelen hun patiënten op basis van de klachten die de patiënt ervaart. Ik weet dat iedereen een wetenschappelijk artikel kan "schrijven" en dat iedereen zijn ervaring kan vertellen maar als Internist kan ik tussen de regels door lezen ,data interpreteren en weet ik wat aannemelijk is en wat niet.. Het was ongelooflijk wat ik las! Er waren ervaringen van mensen die genezen waren van ziekten en klachten van vrijwel alle organen en systemen in het lichaam.

Deze ervaringen zetten me er toe aan de wetenschappelijke literatuur nogmaals te bekijken. Ik las het werk van Dr. James Duke, een prominente plantendeskundige van de Universiteit van Maryland. Hij heeft jarenlang planten beschreven, benoemd en geclassificeerd. Alleen al op basis van de wetenschappelijke literatuur schreef hij meer dan 135 medische indicaties toe aan het gebruik van Mangosteen. Toen Mangosteen juice op de markt kwam was hij al lang met pensioen.

Er was een stapel van ruim een halve meter aan wetenschappelijke onderzoeken, allemaal gedaan door onafhankelijke medische en farmaceutische laboratoria,  zonder onderzoeksgeld van de farmaceutische industrie. De wetenschap bevestigde wat ik had gelezen in de ervaringen. Dit was waar ik  de afgelopen 25 jaar naar op zoek was geweest!

Persoonlijk heb ik ervaren dat Mangosteen juice me meer energie geeft en dat ik me beter kan concentreren, waardoor ik  creatiever ben en beter presteer.

Sommige Mangosteen producten bevatten alleen "extracten" van de vrucht. Natuurlijk kan men dan niet dezelfde resultaten verwachten als wanneer men Mangosteen juice gebruikt van de hele vrucht met alle 40 Xanthonen. 

Les Berenson MD, FACP
Seattle, Washington

Science of the Mangosteen

Before I get to the science below,

I will reference (link) several documents 

I have put together

1) Prevention of Inflammation  Heart Disease and Cancer 

    Includes Annotated Bibliography of Science behind

    Mangosteen and Xanthones

    (PLEASE READ FIRST)

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2) Personal Experiences -

What is a testimonial or personal experience -

Every patient that goes to see their physician provides them

with their own personal experience – (their own testimonial).

The physician based on their judgment, training and insight will interact &

treat the patient that day based on their testimonial (personal experience).

Practitioners DO NOT enter each one of their patients

in randomized controlled trials.

These personal experiences or testimonials should be looked at no differently.

The individuals writing these stories had for the most part already reached

out to the traditional medical model which was unsuccessful.

We should celebrate that a modality exists to help people in such a profound way.

We should also celebrate that Mangosteen juice does so with no toxicity.

As a board certified Internist, I'm excited to be a part of a company

that is willing to share their profits with us as we spread healing

of the Mangosteen around to different countries

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A) Cancer testimonials -

    these defy traditional chemo and radiation therapy

B) Cardiovascular diseases - Congestive Heart Failure and Angina,

    Diabetes, Hypercholesterolemia, Hypertension

C) Brain disorders - Mangosteen & Headaches, Stress, Anxiety,
    Depression, ADD, Autism, Alzheimer's, Parkinsonism, Multiple Sclerosis

D) Arthritis & Autoimmune Disorders -
    back pain, Osteo and Rheumatoid Arthritis, Lupus,
    Fibromyalgia, and Hepatitis C

E) General Conditions - Sleep problems, Loss of Energy & Fatigue,

    safe usage in Pregnancy, PMS, Endometriosis, Menopausal symptoms,

    Children - failure to thrive, Autism, Recovery for West Nile Virus,

F) Skin Conditions - Psoriasis, Eczema, Shingles, Burn Pain relief,

    Toenail Fungus, Herpes, Lichen Planus, Poison Ivy, & fading scars,

G) Personal experiences with Mangosteen

   Variety and collection of case reports on :
   BRAIN disorders - ADD, Depression, Headaches, Alzheimer's
   ARTHRITIS - Acute & Chronic pain relief; Allergies
   SKIN - eczema, burn relief
   URINARY TRACT - safety during dialysis
   GASTROINTESTINAL - Irritable Bowel Syndrome
   DIABETES
   CANCER - pancreatic, Stage 4 Malignant Melanoma, Leukemia,

   Thyroid cancer - (gone in 6 days), Ovarian, Bone Marrow failure - kids, 
   Metastatic Colon Cancer (decreased in 14 days)

Science of the Mangosteen

Fruit

The Mangosteen (Garcinia mangostana) is a tree that is widespread in Southeast Asia. The tree is slow growing, attaining a 20 to 80 foot height. The Mangosteen fruit consists of three parts:
1. Pericarp (peel) - the one-half centimeter-thick purple exterior contains the highest level of xanthone concentration
2. Pulp (fruit) - the delicious inner flesh
3. Seeds

Xanthones

Xanthones are a class of chemicals that are restricted to a relatively small number of plants in nature. They are of taxonomic importance and their pharmacological properties have aroused great interest. Xanthones contain a stable nucleus whereby side chains can form a diversity of chemicals with a variety of pharmacological properties.

Folklore

The fruit is renowned in folklore medicine for its medicinal properties. It has been used for treatment of skin infections, wounds, diarrhea, dysentery, bacteria and fungi.
Antibacterial Introduction
Scientists believe that bacteria have been on the planet for nearly 4,000 million years, making them one of the oldest living organisms. Some bacteria are helpful, but others are among the many germs that can infect our bodies and make us sick. The damage bacteria inflict upon each of the human body's trillions of cells depends on their ability to adhere to, and enter our cells and to deliver toxins.

Antibacterial Research

Scientists from Gifu University in Japan studied the xanthones from the pericarp of the Mangosteen fruit. Their research demonstrated that xanthones from the Mangosteen fruit stopped, "both methicillin-resistant and methicillin-sensitive Staphylococcus aureus". These are common bacteria that causes sever infections within the human body. The authors even suggest that the Mangosteen xanthones may, "find wide pharmaceutical use."
Click here to read the full article and/or the abstract

WHO (World Health Organization) recently listed as the No.2 problem worldwide, MRSA, or methicillin resistant staph aureus, which is in epidemic proportions in the UK among children 2yrs and under. Attached is the full published article in the Journal of Pharmacy and Pharmacology, March 2005 that Dr.Templeman referred to recently about Xanthones that kill penicillin-resistant Staph aureus as well as Vancomycin-resistant enterococci.

Mycobacterium tuberculosis (more commonly known as TB) is relatively unheard of in the United States. However, it is still a common problem in other areas around the world. This bacterium is resistant to many types of medications. In addition, many areas of the world cannot afford modern medicine to fight this strain of bacteria. Therefore, a laboratory in Bangkok Thailand, conducted experiments to ascertain if the Mangosteen xanthones would be beneficial against the TB bacterium. Their research states that the xanthones alpha mangostin, beta mangostin and garcinone B, "exhibited strong inhibitory effect against Mycobacterium tuberculosis."

Click here to read the full article and/or the abstract
Cancer Introduction

Cancer is defined as being a wide range of diseases that are characterized by uncontrolled growth and spread of abnormal cells. Normal cells divide and grow in an orderly fashion, but cancer cells do no. They continue to grow and then begin to crowd out normal cells. Cancer is caused by both external factors (radiation, tobacco, chemicals) and internal factors(inherited, hormones, immune factors). Cancer is a major cause of death in the United States, second only to heart disease in adults, and second only to accidents in children.

• The four most common cancers are lung, breast, prostate, and colon cancer. These four account for 50% of all cancer related deaths.
• Lung cancer is the leading cancer killer.
• Last year there were 1,334,100 new cancer cases
• Since 1990 five million people have died from cancer in the U.S. That equals one person every minute.
• Men have a 1 in 2 chance of developing cancer in their lifetime, while women have a one in 3 risk.
• One in every four deaths is caused by cancer.
• Approximately eight million Americans today have a history of cancer.
• The overall annual costs for cancer equal $107 billion.

Cholesterol Introduction

Cholesterol is a soft, waxy substance that is present in all parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body in the liver and obtained from animal products in the diet. Cholesterol is necessary for normal body functions including the production of hormones, bile acid, and vitamin D. It is transported in the blood to be used by all parts of the body. Cholesterol cannot dissolve in the blood, it has to be transported to and from cells by carriers called lipoproteins. There are two types of lipoproteins:

High-Density Lipoprotein (HDL) is considered the "good" cholesterol because it helps reduce LDL cholesterol levels and keeps the artery walls clean, preventing heart disease.
Low-Density Lipoprotein (LDL) is the major cholesterol carrier in the blood. When there is too much LDL in the blood in slowly builds up within the walls of the arteries that feed the heart and brain. Growing evidence suggests that oxidative damage of LDL leads to atherosclerosis or the build up of plaque on the lining of arteries.

• Typically, the body makes all the cholesterol it needs, so people don't need to consume it. The average man consumes 337 mg of cholesterol per day and the average woman 217 mg.
• Approximately 25% of the adult population has elevated blood cholesterol levels, while more than 50% have levels higher than the "desirable" range.
• Beginning at age 50 a higher percentage of women than men have total blood cholesterol levels of 200 or higher.
• Excessive Cholesterol in the blood contributes to heart disease. In adults total cholesterol levels of 240 or higher are considered to be high, and levels of 200-239 are considered borderline.

Cholesterol Research

• Science has demonstrated that atherosclerosis can be inhibited by limiting the oxidation of LDL. Garcinia mangostana (Mangosteen) contains a xanthone known as mangostin. Mangostin has been shown to act as a free radical scavenger by inhibiting the oxidative change in LDL and thus serves as a potential agent to inhibit atherosclerosis.
  Click here to read the full article and/or the abstract
  Inflammation Introduction
  Inflammation is a process where the body's white blood cells and associated chemical mediators protect our bodies from infection by foreign substances, such as bacteria and viruses. Inflammation is the response of living tissue to damage. Inflammation occurs because of the rapid increase of white blood cells and the symptoms of warmth, redness, swelling, and pain occur as a result of this increased concentration of blood flow. The most common results of inflammation are arthritis, allergies, and headaches
• Arthritis
  Arthritis is caused by the inflammation of the lining of many different joints. Inflammation in the joint lining (the synovium) is what causes the pain, stiffness, and swelling. Symptoms of inflammation include pain, redness, swelling, and the sensation of heat over affected joints.
• One in three Americans has some form of arthritis.
• Arthritis is the leading cause of disability among U.S. adults.
• There are over 100 different kinds of arthritis, but almost all are characterized by inflammation of the joints.
• Allergies/Asthma
  Asthma is the inflammation of the airways and is usually caused by an allergy. When the airways are inflamed, it causes breathlessness. An allergic reaction is a process of inflammation that is caused by a disorder in the immune system. The immune system perceives a substance to be harmful, even though it isn't. The body releases histamine to fight the allergen and it triggers inflammation and symptoms of allergies.
• More than 50 million Americans (about 20% of the population) suffer from allergies each year.
• Approximately 16.7 million people visit a doctor for allergies each year.
• Allergies are the 6th leading cause of chronic disease in the U.S. costing the health care system $18.6 billion annually.
• Headaches
  There are many types and causes of headaches. Many types of headaches are caused by inflammation. For instance, Inflammation of large arteries in the neck and head can lead to vascular headaches-such as migraines. Inflammation from a cold, flu, or sinusitis (inflammation of the sinuses) can also cause headaches. Cluster headaches are caused by inflammation of the nerves.
• 45 million Americans suffer from chronic headaches.
• 1 in 10 people suffer from migraines.
• 6% of men and 18% of women suffer from migraines-that is over 30 million.
• Inflammation Research
  The Mangosteen has been used for centuries by the people of Southeast Asia as an anti-inflammatory agent. More specifically, the pericarp was used to make a tea or poultice. To this day, the Mangosteen is still being used as an anti-inflammatory agent.
• Studies conducted at the University of Madras in India demonstrated that the xanthone mangostin produced anti-inflammatory activity in mice.
  Click here to read the full article and/or the abstract
• Cyclooxygenase (COX) is an enzyme that is responsible for initiating the inflammatory response in the body. This response includes the area of inflammation becoming red, hot, swollen, and painful. Tohoku University in Sendai, Japan demonstrated that the xanthone gamma-mangostin inhibits the COX enzyme, thus inhibiting its inflammatory activity.
  Click here to read the full article and/or the abstract
• Allergies are an immune system reaction to a typically harmless substance. Sometimes your immune system treats a harmless substance (an allergen) as an unwanted invader and it tries to fight it. The overreaction of the immune system is called an allergic reaction and is manifest by the body's tissues becoming inflamed (red, hot, swollen, and painful). Allergies are a characteristic feature of bronchial asthma, rhinitis, and dermatitis.
  Histamine is a chemical the body's cells release when exposed to an allergen, and is responsible for the swelling, red color, and heat associated with an inflammatory response. Xanthones from the Mangosteen fruit help inhibit histamine release and may be useful for treatment of allergies and/or inflammation.
  

PubMed.gov : National Library of Medicine

CLICK HERE to search PubMed.gov in a new window...
THEN, follow the instructions, below:

Put these terms into the Search box and SEE THE EXPLOSION of independent, impartial, 3rd-party INFORMATION!!!

NOTE to Health Professionals: You can use the same search terms, below, in the MedLine database, if you have access, for additional detailed reports.
# of Reports as of February 11, 2005

NOW, just for an interesting contrast, put the following terms into Search box:

Tahitian Noni Juice the by the company Morinda was the previous industry record holder, even though it has barely ANY science backing it up, in comparison!

)

Disclaimer > This information is not intended to treat or cure any disease.
For questions concerning health conditions and the use of dietary supplements, please consult your physician.

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3) Other references :
http://www.mangosteenfruitinfo.com/
Excellent Research Sources

Mangosteen Dosage Guidelines

Alpha mangostin vs Vancomycin resistant Enterococci (VRE) March 2005

WHO (World Health Organization) recently listed as the No.2 problem worldwide, MRSA, or methicillin resistant staph aureus, which is in epidemic proportions in the UK among children 2yrs and under.

Here is the full published article in the Journal of Pharmacy and Pharmacology, March 2005 that Dr.Templeman referred to recently about Xanthones that kill penicillin-resistant Staph areus as well as Vancomycin-resistant enterococci.

Share this information with health professionals and tell them where they can get the highest concentrations of over 40 known xanthones!
____________________________________________________________________________
Alpha mangostin vs Vancomycin resistant Enterococci (VRE) March 2005

Title: Antibacterial activity of [alpha]-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics.

Date: 3/1/2005; Publication: Phytomedicine: International Journal of Phytotherapy & Phytopharmacology; Author: Dharmaratne, H.R.W.

Abstract
[alpha]-Mangostin, isolated from the stem bark of Garcinia mangostana L., was found to be active against vancomycin resistant Enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA), with MIC values of 6.25 and 6.25 to 12.5 [micro]g/ml, respectively. Our studies showed synergism between [alpha]-mangostin and gentamicin (GM) against VRE, and [alpha]-mangostin and vancomycin hydrochloride (VCM) against MRSA. Further studies showed partial synergism between [alpha]-mangostin & commercially available antibiotics such as ampicillin & minocycline. These findings suggested that [alpha]-mangostin alone or in combination with GM against VRE & in combination with VCM against MRSA might be useful in controlling VRE & MRSA infections.

[c] 2004 Published by Elsevier GmbH.
Keywords: Mangostin; Garcinia mangostan; Antibacterial activity; Vancomycin resistant Enterococci; Synergy effect with antibiotics
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Introduction
Enterococci and Staphylococcus aureus are two of the leading causes of nosocomial infections in long-term healthcare facilities. Reports on vancomycin resistant Enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA) infections in hospitals have been increasing worldwide in recent years (Emori and Gaynes, 1993; Leclercq and Courvalin, 1997; Murry, 1997; Moellering, 1998). There are a considerable number of reports on valuable trials carried out to control the infections caused by VRE (Garner, 1996; Slaughter et al., 1996; Montecalvo et al., 1999; Nourse et al., 2000) and MRSA (Coolson, 1995; Cox et al., 1995; Voss et al., 1994; Working Party Report, 1998; Kotilainen et al., 2001). However, further trials would be necessary to discover more reliable methods to adequately control VRE and MRSA infections. In this context, the use of natural products as anti-VRE and anti-MRSA agents would be a promising field on the pathway towards the prevention of VRE and MRSA infections. Further it would be very important to investigate the synergistic behavior of the active natural products with the commercially available antibiotics, with the hope of enhancing their activity.
Garcinia mangostana L. of the family Clusiaceae (Guttiferae) is a tree found in Sri Lanka and other South East Asian countries, which is very popular due to its delicious fruits. Treatment of diarrhea, dysentery, skin infections and as an anti-inflammatory agent are some of the medicinal application of this plant. Xanthones, terpenoids and sugars have been reported from the fruit hulls and leaves of G. mangostana, and some of them have shown a variety of biological activities (Suksamrarn et al., 2002; Mahabusakam and Wiriyachitra, 1987; Praveen et al., 1991). Among them antibacterial activity against MRSA of [alpha]-mangostin is significant (Iinuma et al., 1996). However, no work on anti-VRE activity of [alpha]-mangostin have been reported so far. Therefore, we investigated the anti-VRE activity of [alpha]-mangostin. Further, studies on the synergism between [alpha]-mangostin and commercially available antibiotics against VRE and MRSA strains were also carried out with the hope of prevention of VRE and MRSA infections.
Materials and methods
Extraction and isolation of [alpha]-mangostin and [beta]-mangostin
Stem bark of G. mangostana (1 kg) was dried, powdered and extracted with hexane, methylene chloride and methanol respectively. Silica gel column chromatography of (Fluka 6074, 1 particle size 0.063 [+ or -] 0.2 mm with hexane, methylene chloride and methanol as solvents) of the hexane extract (11.9 g) and methylene chloride extract (25 g) gave two major compounds, [alpha]-mangostin (11.6 g, 1.16%) and [beta]-mangostin (6.4 g, 0.64%) as yellow needles (Fig. 1). These structures were confirmed by the direct comparison with authentic samples and spectral data (Mahabusakam and Wiriyachitra, 1987; Praveen et al., 1991).
Antibiotics
Ampicillin (ABPC), gentamicin (GM), minocycline (MINO) and vancomycin hydrochloride (VCM) were used for the test of synergistic studies.

Test bacteria
VRE: Five strains of VRE (Enterococcus faecalis ATCC 51299, E. faecalis ATCC 51575, E. faecium ATCC 51559, E. faecium KIHC-237 and E. gallinarum KIHC-241) were used in this experiment. Three ATCC strains were purchased from American Type Culture Collection (ATCC). Two strains of E. faecium KIHC-237 and E. gallinarum KIHC-241 were supplied by Kobe Institute of Public Health. The genotypes of E. faecalis ATCC 51299, E. faecium KIHC-237 and E. gallinarum KIHC-241 were van B(+), van A(+) and van Cl(+), respectively. The genotypes of the other VRE such as E. faecalis ATCC 51575 and E. faecium ATCC 51559 were unknown. Minimum Inhibitory Concentrations (MIC) of the five strains of VRE to VCM were measured as 250, 32, 200, 200 and 16 [micro]g/ml, respectively.
[FIGURE 1 OMITTED]
VSE: Three strains of vancomycin-sensitive Enterococci (VSE) (E. faecalis IFO 12965, E. faecium IFO 3535 and E. faecalis ATCC 8459) were used in this experiment. These strains were purchased from the Institute for Fermentation of Osaka (IFO), Japan, and ATCC, respectively.
MRSA: Each of the 3 strains (total: 9 strains) of methicillin-resistant Staphylococcus aureus (MRSA) was kindly donated by Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka National Hospital and Kitano Hospital in 1997. MIC values of nine strains of MRSA to methicillin (DMPPC) were measured as 12.5, 400, 25, 12.5, 400, 1600, 25, 12.5 and 400 [micro]g/ml, respectively.
MSSA: Methicillin-sensitive Staphylococcus aureus (MSSA), Staphylococcus aureus IFO 13276, S. aureus IFO 12732 & S. aureus IFO 3060 were purchased from IFO & used in this experiment.
Broth
SCD broth (Nihon Pharm. Co., Ltd.) was used for pre-incubation of VRE, VSE, MRSA and MSSA. Mueller-Hinton (MH) Agar (Difco Co., Ltd.) was used for the measurement of MIC.

MIC
MIC values were determined by the agar dilution method (Goto et al., 1981) using micro-inoculators (Sakuma Seisakusho Co., Ltd., Tokyo).
Synergism between [alpha]-mangostin and the commercially available antibiotics
A solution (50% dimethylsulfoxide in water) of [alpha]-mangostin alone, and [alpha]-mangostin in combination with respective antibiotics were prepared by the doubling dilution method with sterilized water, and they were poured into sterilized plastic Petri dishes separately. Sterilized MH Agar 8 ml (MH Agar 9 ml was poured into [alpha]-mangostin alone or the antibiotic alone) was poured into the above Petri dishes and mixed. After cooling, the MICs of [alpha]-mangostin, the antibiotics alone and [alpha]-mangostin in combination with each antibiotic, were examined. Through out this experiment, the fraction inhibitory concentration (FIC) indices were calculated by the method used by Didry et al. (1993), and the interactive effects between [alpha]-mangostin and the antibiotics were examined.
Results
Antibacterial activities of [alpha]-mangostin and [beta]-mangostin against VRE and MRSA
Table 1 shows the anti-VRE activity of [alpha]-mangostin and [beta]-mangostin, and Table 2 shows the anti-VRE activity of [alpha]-mangostin and [beta]-mangostin, respectively.
[alpha]-Mangostin was found to be active against five strains of vancomycin-resistant Enterococci (VRE) and nine strains of methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 6.25 and 6.25 to 12.5 [micro]g/ml, respectively.
Synergism between [alpha]-mangostin and the commercial antibiotics
Since [alpha]-mangostin was found to be active against VRE and MRSA, we extended our investigation to study the synergistic effect between [alpha]-mangostin and commercially available antibiotics. FIC index calculations, which is a widely accepted method to evaluate in vitro synergistic studies between different antibacterial compounds were used in our experiments and the results are given in Fig. 2.
Synergism between [alpha]-mangostin and GM against VRE, and [alpha]-mangostin and VCM against MRSA also observed. In the above synergistic studies, the average of FIC indices were calculated as 0.451 [+ or -] 0.069 and 0.441 [+ or -] 0.131, respectively. Partial synergism between [alpha]-mangostin and ampicillin (ABPC), minocycline (MINO), fosfomycin (FOM) and VCM against VRE with FIC indices of 0.606 [+ or -] 0.328, 0.969 [+ or -] 0.217, 0.826 [+ or -] 0.286 and 0.508 [+ or -] 0.271 were observed, respectively.
[FIGURE 2 OMITTED]
[FIGURE 3 OMITTED]
Further, partial synergisms between [alpha]-mangostin and ABPC, GM, MINO and VCM against MRSA were also observed, and their FIC indices were calculated as 0.779 [+ or -] 0.343, 0.667 [+ or -] 0.359, 0.586 [+ or -] 0.303 and 0.504 [+ or -] 0.149, respectively
In VSE, synergism between [alpha]-mangostin and VCM was observed, and the FIC index was calculated as 0.378 [+ or -] 0.113. Partial synergisms between [alpha]-mangostin and the commercially available antibiotics ABPC, GM, MINO and FOM were observed, and their FIC indices were calculated as 0.836 [+ or -] 0.284, 0.500 [+ or -] 0.108, 0.750 [+ or -] 0.000 and 0.792 [+ or -] 0.191, respectively.
On MSSA, FIC indices between [alpha]-mangostin and the commercially available antibiotics ABPC, GM, MINO, FOM and VCM were observed, and their FIC indices were calculated as 0.635 [+ or -] 0.325, 0.428 [+ or -] 0.209, 0.750 [+ or -] 0.000, 0.625 [+ or -] 0.217 and 0.625 [+ or -] 0.000, respectively.
[FIGURE 4 OMITTED]
Synergism between [alpha]-mangostin and GM against 5 strains of VRE, and [alpha]-mangostin and VCM against 9 strains of MRSA were also tested by the evaluation method described by Williamson (2001). The results were shown in Figs. 3 and 4, respectively. Synergism between [alpha]-mangostin and GM against VRE, and [alpha]-mangostin and VCM against MRSA were reconfirmed by this method.
Discussion
In our present study, we have investigated the anti-VRE and anti-MRSA activities of [alpha]-mangostin and [beta]-mangostin, which are the major compounds present in the stem bark extracts of G. mangostana.
Furthermore, the synergistic effect between [alpha]-mangostin and the commercially available antibiotics were investigated. Previous work has also established its excellent activity against MRSA (Iinuma et al., 1996), and above finding led us to investigate its anti-VRE activity and synergism between [alpha]-mangostin and commercially available antibiotics against VRE and MRSA. Activity studies were evaluated by means of MIC. In our previous work on anti-VRE activity and synergistic studies, we reported remarkable anti-VRE and anti-MRSA activities of calozeyloxanthone isolated from Calophyllum moonii, an endemic species from Sri Lanka, against VRE and synergism with the commercially available antibiotics (Sakagami et al., 2002). Our present work on anti-VRE activity and synergistic studies of [alpha]-mangostin clearly shows that its activity is almost similar to that of calozeyloxanthone.
Extended antibacterial activity studies indicated that [alpha]-mangostin and [beta]-mangostin are inactive against gram negative bacteria, such as Escherichia coli IFO 3972. Proteus vulgaris IFO 3988, Serratia marcescens IFO 12648, E. coli O157 (ATCC 43888), Klebsiella pneumoniae IFO 13277 and Pseudomonas aeruginosa IFO 13275 (data not shown).
Our new findings suggested that [alpha]-mangostin alone or in combination with GM against VRE, and in combination with VCM against MRSA, might be useful in controlling VRE and MRSA infections, and should be investigated further in vivo models.
Table 1. MIC values of [alpha]-mangostin and [beta]-mangostin against 5
strains of VRE and 3 strains of VSE

MIC ([micro]g/ml)
[alpha]-mangostin [beta]-mangostin Gentamicin

E. faecalis ATCC 51299 3.13 25 >100
(VRE) (a)
E. faecalis ATCC 51575 3.13 25 >100
(VRE) (a)
E. faecium ATCC 51559 3.13 25 6.25
(VRE) (a)
E. faecium KIHC-237 3.13 25 6.25
(VRE) (b)
E. gallinarum KIHC-241 6.25 25 3.13
(VRE) (b)
E. faecalis IFO 12965 6.25 25 12.5
(VSE) (c)
E. faecium IFO 3535 3.13 25 6.25
(VSE) (c)
E. faecalis ATCC 8459 3.13 25 6.25
(VSE) (c)

(a) Purchased from American Type Culture Collection (ATCC).
(b) Supplied from Kobe Institute of Public Health.
(c) Purchased from Institute for Fermentation of Osaka (IFO), Japan.

Table 2. MIC values of [alpha]-mangostin and [beta]-mangostin against 9
strains of MRSA and 3 strains of MSSA

MIC ([micro]g/ml)
[alpha]-mangostin [beta]-mangostin Gentamicin

MRSA-1 (a) 6.25 >100 25
MRSA-2 (a) 6.25 >100 3.13
MRSA-3 (a) 6.25 >100 1.56
MRSA-4 (b) 6.25 >100 3.13
MRSA-5 (b) 6.25 >100 6.25
MRSA-6 (b) 6.25 >100 0.2
MRSA-7 (c) 6.25 >100 0.2
MRSA-8 (c) 12.5 >100 6.25
MRSA-9 (c) 6.25 >100 >100
MSSA 1 (S. aureus 6.25 >100 0.2
IFO 13276) (d)
MSSA 2 (S. aureus 6.25 >100 0.2
IFO 12732) (d)
MSSA 3 (S. aureus 6.25 >100 0.2
IFO 3080) (d)

(a) Donated from Osaka Medical Center for Cancer and Cardiovascular
Diseases, Japan.
(b) Donated from Osaka National Hospital, Japan.
(c) Donated from Kitano Hospital, Japan.
(d) Purchased from Institute for Fermentation of Osaka (IFO), Japan.
Received 6 May 2003; accepted 22 September 2003
References
Coolson, B., 1995. Aspects of the epidemiology of MRSA in Europe. J. Chemother. 78 (Suppl. 3), 93-98.
Cox, R.A., Conquest, C., Mallaghan, C., Marples, R.R., 1995. A major outbreak of methicillin resistant Staphylococcus aureus caused by a new phage-type (EMRSA). J. Hosp. Infect. 29, 87-106.
Didry, N., Dubreuil, L., Pinkas, M., 1993. Microbiological properties of protoanemonin isolated from Ranunculus bulbosus. Phytother. Res. 7, 21-24.
Emori, T.G., Gaynes, R.P., 1993. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin. Microbiol. Rev. 6, 428-442.
Garner, J.S., 1996. Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infect. Control Hosp. Epidemiol. 17, 53-80.
Goto, S., Yo, K., Kawakita, R., Kosakai, N., Mitsuhashi, S., Nishino, T., Ohsawa, N., Tanami, H., 1981. Re-revision of the method of Minimum Inhibitory Concentration (MIC). Chemotherapy 29, 76-79.
Iinuma, M., Tosa, H., Tanaka, T., Asai, F., Kobayashi, Y., Shimano, R., Miyauchi, K., 1996. Antibacterial activity of xanthones from Guttiferaeous plants against methicillin-resistant Staphylococcus aureus. J. Pharm. Pharmacol. 48, 861-865.
Kotilainen, P., Routamaa, M., Peltonen, R., Evesti, P., Eerola, E., Salmenlinna, S., Vuopio-Varkila, J., Rossi, T., 2001. Eradication of methicillin resistant Staphylococcus aureus from a health center ward and associated nursing home. Arch. Intern. Med. 161, 859-863.
Leclercq, R., Courvalin, P., 1997. Resistance to glycopeptides in Enterococci. Clin. Infect. Dis. 24, 545-556.
Mahabusakam, W., Wiriyachitra, P., 1987. Chemical constituents of Garcinia mangostana. J. Nat. Prod. 50, 474-478.
Moellering, R.C., 1998. Vancomycin-resistant Enterococci. Clin. Infect. Dis. 26, 1196-1199.
Montecalvo, M.A., Jarvis, W.R., Uman, J., Shay, D.V., Petrullo, C., Rodney, K., Gedris, C., Horowitz, H.W., Wormser, G., 1999. Infection-control measures reduce transmission of vancomycin-resistant Enterococci in an endemic setting. Ann. Intern. Med. 131, 269-272.
Murry, B., 1997. Vancomycin-resistant Enterococci. Am. J. Med. 101, 284-293.
Nourse, C., Byrne, C., Murphy, H., Kaufman, M.E., Clarke, A., Butler, K., 2000. Eradication of vancomycin-resistant Enterococcus faecium from a pediatric oncology unit and prevalence of colonization in hospitalized and community-based children. Epidemiol. Infect. 124, 53-59.
Praveen, M., Khan, N.U., Achari, B., Dutta, P.K., 1991. A triterpene from Garcinia mangostana. Phytochemistry 30, 361-362.
Sakagami, Y., Kajimura, K., Wijesinghe, W.M.N.M., Dharmaratne, H.R.W., 2002. Antibacterial activity of Calozeyloxanthone isolated from Calophyllum species against Vancomycin-resistant Enterococci (VRE) and synergism with antibiotics. Planta Med. 68, 541-543.
Slaughter, S., Hayden, M.K., Nathan, C., Hu, T.C., Rice, T., van Voorhis, J., Matushek, M., Franklin, C., Weinstein, R.A., 1996. A comparison of the effect of universal use of gloves and gowns with that of glove use alone on acquisition of vancomycin-resistant Enterococci in a medical intensive care unit. Ann. Intern. Med. 125, 448-456.
Suksamrarn, S., Suwannapoch, N., Ratananukul, P., Aroonlerk, N., Suksamrarns, A., 2002. Xanthones from green fruit hulls of Garcinia mangostana. J. Nat. Prod. 65, 761-763.
Voss, A., Milatovic, D., Wallrauch-Schwarz, C., Rosdahl, V.T., Braveny, I., 1994. Methicillin resistant Staphylococcus aureus in Europe. Eur. J. Clin. Microbiol. 13, 50-55.
Williamson, E.M., 2001. Synergy and other interactions in phytomedicines. Phytomedicine 8, 401-409.
Working Party Report, 1998. Revised guideline for the control of methicillin resistant Staphylococcus aureus infection in hospitals. J. Hosp. Infect. 39, 253-255.
Y. Sakagami (a,*), M. Iinuma (b), K.G.N.P. Piyasena (c), H.R.W. Dharmaratne (c)
(a) Osaka Prefectural Institute of Public Health, Osaka, Japan
(b) Gifu Pharmaceutical University, Gifu, Japan
(c) Natural Products Programme, Institute of Fundamental, Studies, Kandy, Sri Lanka

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