STIMUNO Phyllanthus Niruri L. 25mg / 5mL Syrup 60mL

Store at temperatures not exceeding 30°C. Protect from light.
Shelf-Life: 36 months.

 

Introduction: Stimuno is made from extract of Phyllanthus niruri L. In some region in Indonesia, this plant is known as meniran. Since 2000 years ago, Phyllanthus niruri L. has been widely used as herbs in various countries in the world, one of them is 'Ayurvedic Medicine/Ayurveda' in India. The use of this plant is very broad, eg, for treating hepatitis, gonorrhea, urinary tract infections, stomachache, toothache, kidney stones, irregular period (menstruation), diabetes, dysentery and also as an antipyretic and diuretic.
The genus of Phyllanthus comprises of some species, 2 of the most common species usually made into herbs are Phyllanthus niruri L. and Phyllanthus urinaria. Phyllanthus niruri L. has pale green stalks, whereas Phyllanthus urinaria has reddish stalks. In some countries, Phyllanthus niruri L. is known as Phyllanthus amarus, Phyllanthus debilis, Phyllanthus fraternus or Phyllanthus rotundifolius.
The activity of the plant on immune system has been tested in several preclinical studies. Further preclinical studies in rats and mice were conducted to determine the safety and immunomodulatory characteristics of Phyllanthus niruri L. The results of the studies showed that the extract of Phyllantus niruri L. can modulate the immune system through proliferation and activation of T and B lymphocytes, secretion of specific cytokines eg, interferon-γ, TNF-α (tumor necrosis factor-α), interleukin and activation of complement system, phagocytes eg, macrophages and monocytes. In addition, the cytotoxic activity of natural killer (NK) cells is increased. Furthermore, several clinical studies have been conducted to assess immunomodulatory effects in some cases with certain conditions, eg, pulmonary TB (tuberculosis), hepatitis B, upper respiratory tract infections, herpes zoster, acute exacerbation of chronic obstructive pulmonary diseases (COPD) and vaginal candidiasis. From preclinical and clinical studies similar results were found in immunological parameter, which is P. niruri L. extract in Stimuno acts as immunomodulator, to strengthen the body immune system and increase success rate in infection therapy.
Stimuno is the only immunomodulator with phytopharmaca certificate from Indonesian National Agency for Drug and Food Control. Phytopharmaca certificate is given only to herbal products, containing standardized extract, with efficacy proven by clinical trial, hence it shows comparable efficacy to synthetic drugs. Stimuno got the phytopharmaca certificate after going through 4 stages of trial, ie, 1st stage, preclinical trial to study the safety (ie, toxicity studies) and efficacy (ie, pharmacodynamic studies) in animals; 2nd stage, simple standardization of raw material; 3rd stage, pharmaceutical standardization to ensure the identity and standardization of finished goods; 4th stage, clinical trials in both healthy volunteers and patients. In conclusion, as phytopharmaca product, Stimuno is certified for its quality, safety and efficacy.
Stimuno has been marketed since 1999 as prescribed product in Indonesia. Stimuno received good responses from doctors for its quality and safety. Since August 1st, 2005, Stimuno was switched to over-the-counter (OTC) allowing customers to buy from outlets without prescriptions. This new approach is welcome by customers as they have been aware on the efficacy and safety of the product since the prescription period.
Pharmacology: Pharmacodynamics: Mechanism of Action: Stimuno activates both specific and non-specific immune system, and also both cellular and humoral immune system.

Toxicology: Preclinical Safety Trial: Acute Toxicity: Phyllanthus niruri L. extract is classified as PNT (Practically Non-Toxic), because organ disorders and death of 50% animal trial population only occurred after oral administration of Phyllanthus niruri L. extract with dose of 14 g/kg body weight for 24 hrs in BALB/c strain mice.
Subchronic Toxicity: Oral administration of Phyllanthus niruri L. extract with dose of 2, 3, 4, 5 g/kg body weight/day for 12 weeks in Wistar rats showed none had pathological and histopathological abnormality in pulmonary, liver, lymph, intestine and muscle.
Chronic Toxicity: Oral administration of Phyllanthus niruri L. extract on Sprague-Dawley strain rats with dose 66.95, 267.8, and 1071.2 mg/kg body weight/day for 6 months does not interfere behavior, motor activity, hepatic function, renal function, blood biochemical, body weight, organ index and also macroscopic and histopathology of some organs.
Teratogenicity: Teratogenicity test was done on Wistar rats at 3 dose-ranging regimens ie, lowest dose (equivalent to usual dose in human), mid-dose (equivalent to the dose of 4 times usual dose in human) and the highest dose (equivalent to the dose of 16 times usual dose in human). In control group, all fetuses were alive. In the lowest dose group, mean number of living fetuses per animal was comparable to that of the control group, but with 6.25% resorption observed. Increasing dose was not accompanied by increased resorption (at the mid-dose, there was 3.23% resorption observed on the fetuses, and at the highest dose, 1.35%). The result showed that at the lowest dose (66.95 g/kg BW in rats or equivalent to the usual dose in human), there was no tissue abnormality observed on the tested fetuses. However, at the highest dose, formation of aberrant tissues on the face (forehead section), hydrocephalus and no covering tissue formation at the abdomen were found, each on different fetuses of different forebears. Even though Phyllanthus niruri L. extract is safe at human usual dose, but in the light of the teratogenicity trial result, the extract should be used with caution in pregnant women considering that at the high dose, the extract risked the fetus.
Clinical Safety Trial: Based on clinical trial, long-term use (6 months) in pulmonary TB patients do not show clinically significant side effect.
In 1 study, after oral administration of Phyllanthus niruri L. with dose of 2 capsules twice daily for 12 weeks, showed that Phyllanthus niruri L. extract was well tolerated and safe for chronic hepatitis B patients, with an incident of adverse events similar to placebo. No serious adverse events occur during the study. The majority of adverse events were mild. The most common adverse events were headache, fatigue, cold, hyperurinaria and loss of appetite. Of them, only hyperurinaria and loss of appetite were possibly related to Phyllanthus treatment. At the end of the study, all the adverse events were already resolved.
After oral administration of Phyllanthus niruri L. extract with dose of 3x50 mg/day for 2 weeks, it showed that Phyllanthus niruri L. extract was well tolerated and safe for COPD patients.
A clinical trial was conducted to investigate the effectiveness and safety of Phyllanthus niruri L. extract in combination with standard therapy for patients with uncomplicated herpes zoster. After oral administration of Phyllanthus niruri L. extract with dose of 50 mg for 15 days, it showed that adverse event were not significantly different between 2 groups. The most common adverse events were diuresis and hypotension.
Based on clinical trial which conducted to investigate the role of Phyllanthus niruri L extract in the treatment of upper respiratory tract infection in pediatric patients, it showed that Phyllanthus niruri L. extract was well-tolerated and safe. This study was conducted for 7 days.
A clinical trial was completed to compare the effectiveness of ketoconazole alone with ketoconazole combined with Phyllanthus niruri L. extract in the treatment of vaginal candidiasis. After oral administration of Phyllanthus niruri L. extract with dose of 2 capsules (100 mg) 3 times a day for 7 days, it showed that Phyllanthus niruri L. extract was well-tolerated and safe for vaginal candidiasis patients.
The study was conducted to investigate the role of Phyllanthy herba as an adjuvant therapy to some tropical skin disease eg, varicella-zoster infection and leprosy. The study was conducted from May 2000 until March 2002 in Manado. After oral administration of Phyllanthus niruri L. extract with dose of 3x50 mg/day, no patients perform any adverse reactions.
Overview on Immune System: The cells and molecules responsible for immunity constitute the immune system, and their collective and coordinated response to the introduction of foreign substances is called the immune response. The physiologic function of the immune system is defense against infectious microbes. Immunity is a reaction to foreign substances, including microbes, as well as to macromolecules eg, proteins and polysaccharides, regardless of the physiologic or pathologic consequence of such a reaction.
Innate and Adaptive Immunity: Defense against microbes is mediated by the early reactions of innate immunity and the later response of adaptive immunity. Innate immunity (natural or native immunity) consists of cellular or biochemical defense mechanisms that are in place even before infection and poised to respond rapidly to infections. These mechanisms react only to microbes and not to noninfectious substances and they respond in essentially the same way to repeated infections. The principal components of innate immunity are: Physical and chemical barriers eg, epithelia and antimicrobial substances produced at epithelial surfaces, phagocytic cells (neutrophils, macrophages) and NK cells. Blood proteins, including members of the complement system and other mediators of inflammation, proteins called cytokines that regulate and coordinate many of the activities of the cells of innate immunity.
Innate immunity provides the early lines of defense against microbes. In contrast to innate immunity, there are other immune responses that are stimulated by exposure to infectious agents and increase in magnitude and defensive capabilities with each successive exposure to a particular microbe. Because this form of immunity develops as a response to infection and adapts to the infection, it is called adaptive immunity. The defining characteristics of adaptive immunity are exquisite specificity for distinct molecules and an ability to "remember" and respond more vigorously to repeated exposures to the same microbe. The adaptive immune system is able to recognize and react to a large number of microbial and nonmicrobial substances. In addition, it has an extraordinary capacity to distinguish among different, even closely related, microbes and molecules, and for this reason, it is also called specific immunity. It is also sometimes called acquired immunity, to emphasize that potent protective responses are "acquired" by experience. The components of adaptive immunity are lymphocytes and their products. Foreign substances that induce specific immune responses or are the targets of such responses are called antigens.
Innate and adaptive immune responses are components of an integrated system of host defense in which numerous cells and molecules function cooperatively. The mechanisms of innate immunity provide effective defense against infections. However, many pathogenic microbes have evolved to resist innate immunity, and their elimination requires the powerful mechanisms to adaptive immunity. There are 2 important links between innate immunity and adaptive immunity. First, the innate immune response to microbes stimulates adaptive immune responses and influences the nature of the adaptive responses. Second, adaptive immune responses use many of the effector mechanisms of innate immunity to eliminate microbes, and they often function by enhancing the antimicrobial activities of the defense mechanisms of innate immunity.
Type of Adaptive Immune Responses: There are 2 types of adaptive immune responses, called humoral immunity and cell-mediated immunity, that are mediated by different components of the immune system and function to eliminate different types of microbes. Humoral immunity is mediated by molecules in the blood and mucosal secretions, called antibodies, that are produced γ-cells called B lymphocytes (B-cells). Antibodies recognize microbial antigens, neutralize the infectivity of the microbes, and target microbes for elimination by various effector mechanism. Humoral immunity is the principal defense mechanism against extracellular microbes and their toxins because secreted antibodies can bind to these microbes and toxins and assist in their elimination.
Cell-mediated immunity, also called cellular immunity, is mediated by T lymphocytes (T-cells). Intracellular microbes eg, viruses and some bacteria, survive and proliferate inside phagocytes and other host cells, where they are inaccessible to circulating antibodies. Defense against such infections is a function of cell-mediated immunity, which promotes the destruction of microbes residing in phagocytes or the killing of infected cells to eliminate reservoirs of infections.