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Composition:

Each sachet contains Carica papaya leaf extract 350mg + Tinospora cordifolio extract 150mg + Goat milk powder 100mg + Vitamin E 40mg.

Indication:

In thrombocytopenia & Low WBC count associated with Denque, Malaria, Immune Thrombocytopenia and Acute Microbial Infection.

Dosages:

Platelet Count Above 50000/mcl : 1 sachet BID. For Platelet Count below 50000/mcl: 2 sachet BID.

 

 

Clinical Trials:

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Trials with Carica Papaya

Direct effects of Carica papaya leaf extract on platelets during Dengue

The processes involved in platelet activation and Thrombocytopenia in dengue cases have been poorly understood. The treatment of dengue is not properly defined; however, extracts of Carica papaya have emerged as one of the preferred therapeutic options. Researchers have posited that extract of Carica papaya leaf may help in recovering the platelet count in such individuals. However, the mechanisms with which the plant extract recovers the platelets are yet to be elucidated. A study was conducted with an objective to evaluate the effects of Carica papaya leaf extract, in terms of its direct/indirect action on platelets and platelet aggregation during dengue viral infection. The authors recruited 60 dengue positive and 60 healthy subjects. Platelet-Rich Plasma and Platelet-Poor Plasma were collected from both the dengue infected and healthy control blood samples and effects of the leaf extract was assessed on plasma as well as platelets. It was observed that platelet aggregation remarkably reduced when leaf extract preincubated with dengue plasma was added into control Platelet-Rich Plasma. Whereas, when leaf extract incubated-control plasma was added into control Platelet-Rich Plasma, no change was observed in aggregation. Moreover, even the direct addition of Carica papaya leaf extract induced a significant reduction in platelet aggregation in both dengue Platelet-Rich Plasma and control Platelet-Rich Plasma. Within the dengue group, decrease in aggregation was similar in Platelet-Rich Plasma obtained from severe and non-severe cases.

The authors of the study concluded that extract of Carica papaya leaf exerts direct effect on platelets and that these possesses a dengue-specific neutralizing effect on dengue viral-infected plasma, which may confer a protective role on platelets.

Source: Chinnappan S, Ramachandrappa VS, Tamilarasu K, Krishnan UM, Balakrishna Pillai AK, Rajendiran S. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study. Viral Immunol. 2016 Apr;29(3):164-8.

Role of Carica papaya in inducing synthesis of in vitro Thrombopoietic Cytokines

The extracts of Carica papaya leaf have been reported to increase the Thrombocyte counts in individuals with dengue. A study was conducted in order to analyze the potential of Carica papaya to induce Thrombopoietic Cytokines [Interleukin-6 and stem cell factor]. Stem cells obtained from human exfoliated deciduous teeth and in vitro cultures of Peripheral Blood Leukocytes were exposed to unripe papaya pulp juice.

The results of the study revealed that a rapid in vitro scratch gap closure was achieved in human exfoliated deciduous tooth culture treated with unripe papaya pulp juice. An increase was observed in the concentrations of Interleukin-6 in human exfoliated deciduous tooth culture and Peripheral Blood Leukocytes culture supernatant when treated with unripe papaya. Moreover, a significant rise in synthesis of stem cell factor (when treated with unripe papaya) in human exfoliated deciduous tooth culture was also noted.

The conclusion drawn from the study suggests that unripe papaya possess the potential to induce and upregulate in vitro Thrombopoietic cytokines synthesis in cells of hematopoietic and mesenchymal origin (both in Peripheral Blood Leukocytes and human exfoliated deciduous tooth culture).

Source: Aziz J, Abu Kassim NL, Abu Kasim NH, Haque N, Rahman MT. Carica papaya induces in vitro thrombopoietic cytokines secretion by mesenchymal stem cells and haematopoietic cells. BMC Complement Altern Med. 2015 Jul 8;15:215.

A case presentation on the effect of papaya leaves extract oral preparation on Thrombocyte counts in Dengue

The incidence of dengue fever is rising in developing nations like India, Pakistan, Sri Lanka and Bangladesh. The disease management is still lacking in terms of the use of antiviral chemotherapy or vaccine for dengue virus and is solely dependent on supportive measures. The decrease in the Thrombocyte count leads to Dengue Hemorrhagic Fever and leads to number of complications and mortality. Carica papaya leaves extract oral administration is posited to have a positive impact on thrombocyte count. The authors of the study describe a case study The authors of the study describe a case of a 23-year-old male, a medical student from Karachi, who was brought to a local clinic with a fever of 102°F for the preceding 2 days. Symptoms included nausea, erythema of the skin, severe body pain and fatigue. The subject also revealed that he was bitten by a mosquito somewhere. The subject was admitted and tested for typhoid, malaria and dengue. Dengue Rapid N51 antigen was found to be positive. The hematological reports also demonstrated an abrupt decline in the patient’s thrombocyte counts. After obtaining patient’s consent regarding the treatment, Carica papaya leaves extract was given orally to examine the popular belief of the leaves increasing thrombocyte counts. Blood samples were evaluated for complete blood count before and after the administration of the juice. The investigation conducted revealed increased Thrombocyte count from 28000/micro liter to 138000/micro liter at the end of five days.

Therefore, this study concluded the beneficial role of Carica papaya extract in increasing the Thrombocyte count, thereby improving the rate of prognosis of Dengue.

Source: Siddique O, Sundus A, Ibrahim MF. Effects of papaya leaves on thrombocyte counts in dengue–a case report. J Pak Med Assoc. 2014 Mar;64(3):364-6.

Carica papaya leaves juice increases the platelet count in patients with Dengue Fever and Dengue Hemorrhagic Fever

A study was conducted to assess the platelet enhancing property of Carica papaya leaves Juice in patients with dengue fever. The study involved 228 patients with Dengue Fever and Dengue Hemorrhagic Fever. Half the patients were administered the Carica papaya leaves Juice for 3 consecutive days while the others remained as controls and were given the standard management. The study patient’s full blood count was monitored every 8 hours for 48 hours. Gene expression studies were also conducted on the Arachidonate 12-lipoxygenase (ALOX-12) and Platelet-activating factor receptor (PTAFR) genes. The repeated measure analysis of co-variance was used to calculate the mean increase in platelet counts and thereby compared in both the groups. Interventional group showed significant increase in mean platelet count but not in the control group 40 hours since the first dose of Carica papaya leaves juice. The comparative study reported significantly higher mean platelet count in intervention group than control group after 40 and 48 hours of admission. Interventional group also had a very high expression of the ALOX -12 (FC = 15.00) and PTAFR (FC = 13.42) genes.

Hence, it was concluded that Carica papaya leaves Juice significantly increases the platelet count in patients with dengue fever and Dengue Hemorrhagic Fever.

Source: Subenthiran S, Choon TC, Cheong KC, Thayan R, Teck MB, Muniandy PK, Afzan A, Abdullah NR, Ismail Z. Carica papaya Leaves Juice Significantly Accelerates the Rate of Increase in Platelet Count among Patients with Dengue Fever and Dengue Haemorrhagic Fever. Evid Based Complement Alternat Med. 2013;2013:616737.

Therapeutic use of extracts from plant Carica Papaya

Dengue virus belongs to the genus Flavivirus and family Flaviviridae. Dengue virus is most commonly known to cause Dengue Hemorrhagic Disease which has become a public health problem across the globe. The non-structural 2B and 3 (NS2B-NS3) protease complex of the virus is thought to be responsible for the replication of virus. Therefore this complex is considered to be a reliable anti-viral target.

The leaf extracts of Carica papaya are generally recommended as a therapeutic agent for the management of patients with dengue fever. However, there is lack of scientific evidences for its anti-dengue properties. Therefore, the investigators planned to explore the anti-viral activity of the compounds present in the leaves of Carica papaya against Dengue 2 virus. They analyzed the anti-dengue activities of the extracts from the plant with the help of bioinformatics tools.

The investigators explored that the flavonoid quercetin had highest binding energy against NS2B-NS3 protease complex; evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. The results thus concluded that the flavonoids from Carica papaya have significant anti-dengue activities.

Source: Senthilvel P, Lavanya P, Kumar KM, et al. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly. Bioinformation. 2013;9(18):889-895.

Erythrocyte membrane stabilization property of the plant Carica papaya

The fruit juice and leaf extracts from the plant Carica papaya leaf are known to encompass several beneficial medical properties. Some recent reports have claimed the fruitful effects of Carica papaya leaf juice in curing patients with Dengue viral infection. The objective of the present study was to evaluate the membrane stabilization potential of Carica papaya leaf extracts using an in vitro hemolytic assay. The study was carried out between the month of June and August 2010. About 2 milliliters of blood from healthy volunteers and patients with serologically confirmed current dengue infection were freshly collected and used in the assays.

The fresh papaya leaves at three different maturity stages (immature, partly matured, and matured) were cleaned with distilled water, crushed, and the juice was extracted with 10 ml of cold distilled water. The freshly prepared cold water extracts of papaya leaves (1 ml containing 30 μl of papaya leaf extracts, 20 μl from 40% erythrocytes suspension, and 950 μl of phosphate buffered saline) were used in the heat-induced and hypotonic-induced hemolytic assays. Six different concentrations (9.375, 18.75, 37.5, 75, 150, and 300 μg/ml) of freeze dried extracts of the partly matured leaves were used in dose response experiments. Moreover, the membrane stabilization properties were examined with heat-induced and hypotonicity-induced hemolysis assays. Results of the study divulged the following:

  • Extracts of papaya leaves of all three maturity levels showed a momentous reduction in heat-induced hemolysis compared to controls
  • Papaya leaf extracts of all three maturity levels demonstrated more than 25% inhibition at a concentration of 37.5 μg/ml
  • The highest inhibition of heat-induced hemolysis was observed at 37.5 μg/ml
  • Inhibition activity of different maturity levels was not considerably different from one another
  • Heat-induced hemolysis inhibition activity did not demonstrate a linear dose response relationship
  • A marked inhibition of hypotonicity-induced hemolysis was observed at 37.5 μg/ml concentration of the extract.

It was thus concluded that Carica papaya leaf extracts depicted a momentous inhibition of hemolysis in vitro and could have a potential therapeutic effect on disease processes causing destabilization of biological membranes.

Source: Ranasinghe P, Ranasinghe P, Abeysekera WPKM, et al. In vitro erythrocyte membrane stabilization properties of Carica papaya L. leaf extracts. Pharmacognosy Research. 2012;4(4):196-202.

Salutary effects of Carica papaya leaf extract: Benefits in dengue

Dengue, a mosquito-borne infection is a public health problem, spanning all tropical and sub-tropical geographic regions across the globe, mainly the urban and semiurban areas. The hallmark feature of dengue fever is a sudden drop in the platelet count which is responsible for fatal complications such as Dengue Haemorrhagic Fever. As per the Ayurvedic literature, Carica papaya leaf extracts exhibits hemostatic and other medicinal properties, which may be potentially beneficial in this condition. A pilot study was conducted to confirm if Carica papaya leaf extract had any effect on improving the falling platelet count in dengue patients.

Patients meeting all the following inclusion criteria were labeled as having dengue fever and were recruited for the study: (1) Patients from dengue prevalent region at time of a dengue epidemic (2) Fever of ≥ 3-day duration. (3) Strong clinical suspicion of dengue (4) Platelet count <130000 per mm3. Twelve patients met these criteria and were given a drink of papaya leaf extract-two 5ml doses at an 8 hour interval for adults and two 2.5 ml doses at an 8 hour interval for children. Before drinking papaya leaf juice, a sample of blood was drawn to evaluate the white cell count, platelet count, alanine aminotransferase and packed cell volume. Another sample was drawn on the subsequent day to re-evaluate these counts. Tests were done using an automated system

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and confirmed manually. The Pre and Post treatment clinical condition was also assessed. The patients were observed for adverse effects for about 14 days and were asked to notify at the earliest in case any abnormal symptoms appeared. Pharmacotherapeutic agents known to alter the platelet count such as blood products, prednisolone or non-steroidal antiinflammatory drugs were not given to these patients.

The results demonstrated a rise in the platelet counts as well as the total white cell counts in all 12 patients within 24 hours of papaya leaf juice consumption. Moreover, all patients recuperated soon, without the need of admitting to hospital. Eight patients did not have a notable increase in the packed cell volume or the Serum Glutamic-Pyruvic Transaminase levels at the time of intervention. Four patients with elevated Serum Glutamic-Pyruvic Transaminase had their counts reduced by 1/3 in the second day after intervention. Five patients with Platelet Count < 100000 had itching, hemorrhagic skin rash which improved within 48 hours of treatment with this natural product.

Hence, this study provides compelling evidence in favor of the efficacy of Papaya leaf juice in increasing the total white cell counts, platelet counts without hospital admission.

Source: Hettige S. Salutary effects of carica papaya leaf extract in dengue fever patients– a pilot study. Sri Lankan Family Physician. 2008;29:17-19.

Trials with Tinospora cordifolia:

Tinospora cordifolia stem containing Cordifolioside-A exhibits radioprotective and Cytoprotective Potential

Literature is inundated with reports suggesting Tinospora cordifolia to have Immunostimulant, Hepatoprotective, Diuretic, Anti-inflammatory, Radioprotective, Antioxidant, Hypoglycemic, and Antipyretic activity. A study was conducted to shed light on the Radioprotective and Cytoprotective effects of Cordifolioside-A, the main active ingredient of n-butanol fraction of Tinospora cordifolia against 4 Gy- radiation in experimental models and Cyclophosphamide induced genotoxicity.

Presence of cordifolioside-A in n-butanol fraction of Tinospora cordifolia stem ethanolic extract was corroborated by High Performance thin layer chromatography analysis. Radioprotective potential was assessed at 80 and 120 mg/kg, intraperitoneal (i.p.) dose of n-butanol fraction of Tinospora cordifolia administered 15 days before whole body radiation exposure by recording survival rate, increase/decrease in body weight, hematology, Spleen Colony Forming Unit, and micronucleus expression. The authors also validated the cytoprotective potential of n-butanol fraction of Tinospora cordifolia at 5, 10, and 15 mg/ml concentrations on Allium cepa root meristem growth against cyclophosphamide.

The results demonstrated that n-butanol fraction of Tinospora cordifolia (120 mg/ kg, i.p.) afforded considerable protection against radiation as seen by increased survival rate, body weight retention, hematological variables, Spleen Colony Forming Unit assay, and reduced micronucleus expression. The cytoprotective activity peaked at 10 mg/ml n-butanol fraction of Tinospora cordifolia concentration with a noteworthy increase in root growth, non-toxic mitotic index (65.9%) and lesser chromosomal abnormalities (15.4%). n-butanol fraction of Tinospora cordifolia at 10 mg/ml concentration showed very few C-anaphase compared to aberrations like fragmentation, C-anaphase, multipolarity and sticky chromosome in cyclophosphamide alone.

The authors of this study confirmed that n-butanol fraction of Tinospora cordifolia containing cordifolioside-A has notable Radioprotective and Cytoprotective properties.

Source: Patel A, Bigoniya P, Singh CS, Patel NS. Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A. Indian Journal of Pharmacology. 2013;45(3):237-243.

Beneficial role of Tinospora cordifolia in the treatment of hyper-reactive malarious splenomegaly

Malaria corresponds to one of the major health issues worldwide. Several treatment strategies have evolved in managing this entity but its prevalence still remains cumbersome. Singh et al examined the impact of aqueous extract of Tinospora cordifolia, an antimalarial immunomodulator along with chloroquine in countering hyper-reactive malarious splenomegaly. A cohort of individuals affected with malaria who were partial/ slow responders to the conventional antimalarial agent, i.e. chloroquine, were enrolled.

Aqueous extract of Tinospora cordifolia was combined with chloroquine base weekly and these patients were kept under observation for six months. Parameters such as spleen enlargement, Hb, serum IgM and overall improvement in the health were measured.

The results divulged that by adding the extract of Tinospora cordifolia to the standard regime showed regression in the size of spleen up to 37-50% after six weeks and 45-69% after six months (Figure 1). Additionally, decrease in the IgM count and increase in Hb levels were observed. The overall well-being of the affected individuals also showed gradual improvement.

 

figure1

 

Therefore, combined therapy of Tinospora cordifolia and chloroquine paves a new way in the management of hyper-reactive malarious splenomegaly.

Source: Singh RK. Vector J. Tinospora cordifolia as an adjuvant drug in the treatment of hyper-reactive malarious splenomegaly–case reports. Borne Dis. 2005 Mar;42(1):36-8.

Trials with Vitamin E:

Beneficial effect of vitamin E and C on platelet levels in Dengue fever

Keeping in mind the menace of dengue, a study was conducted to appraise the beneficial effects of Vitamins E and C on Thrombocytopenia in dengue patients. The researchers collected blood samples of 48 patients suspected to have dengue. ELISA was performed to detect serum antibodies IgG and IgM. In addition, hemogram and complete blood count of the samples were also carried out. Of the 48 suspected cases, 27 were diagnosed for dengue, and subsequently were supplemented with Vitamins E and C consistent with the prescribed limit for eight days. Baseline hemoglobin (Hb) and platelet count was evaluated on the first day of supplementation as well as on the eighth day. The results revealed mean Hb values to be 10.2 ± 0.4 gm/dl and 10.9 ± 0.3 gm/dl, on day 1 and day 8, respectively. Mean platelet counts on day 1 and day 8 were 1.8 ± 0.3 × 105 and 2.3 ± 0.5 × 105, respectively (Figure 2). The results were suggestive of a favorable role of Vitamins E and C supplementation in augmenting the platelet count, thereby aiding in early recovery in dengue fever.

 

figure2

 

Source: Chandra P, Sharma H, Gupta A, Rai Y. Role of antioxidant vitamin E and C on platelet levels in dengue fever. International Journal of Basic and Applied Medical Sciences. 2013; 3(1): 287-291.

Function of micronutrients in Dengue Fever

Dengue fever is the most common vector-borne viral infection in humans. Over time, it has emerged as a public health challenge. There is lack of definitive treatment and vaccine for this infection. It is believed that host factors such as alteration in the nutritional status may help in impeding disease progression. Nutritional modulation has been useful in other infections, and it is an economic method for interrupting transmission, reducing vulnerability and reducing disease severity. The present study evaluated the role of micronutrients in Dengue Virus infection. The results showed that Vitamin E and D supplementation may prove useful for treatment of Dengue Virus infection. Furthermore, Vitamin E supplementation seemed to be effective and simple. The ability of vitamin E to alleviate oxidative stress and leucopenia in laboratory studies may be identified as plausible mechanisms by which Vitamin E aids in reducing the severity of dengue virus infection.

Source: Ahmed S, Finkelstein JL, Stewart AM, Kenneth J, Polhemus ME, Endy TP, Cardenas W, Mehta S. Micronutrients and dengue. Am J Trop Med Hyg. 2014 Nov;91(5):1049-56.

Trials with Goat milk

Nutritious value of goat milk and its products in management of Dengue fever

Dengue fever has attained epidemiological proportions in India. The infection is primarily transmitted to humans by Aedes aegypti mosquito. Patients with dengue fever often have high body temperature, redness in eyes, restlessness and cold clammy skin. Selenium deficiency and significant decrease in platelet count are two main complications of dengue fever. If the platelets decrease below 20,000, there is an emergent need for platelet transfusion. Goat milk and milk products are being increasingly recognized as agents useful for treating dengue fever. Goat milk may help in maintaining fluid balance of the body. Additionally, it aids in digestive and metabolic utilization of calcium, phosphorus and magnesium. It is important to note that goat milk is a rich source of selenium as compared to cow and sheep milk. The intake of goat milk in dengue helps in modulation of human immune responses. Therefore, goat milk and its products appear to be useful for management of dengue fever.

Source: Mahendru G, Sharma PK, Garg VK, Singh AK, Mondal SC. Role of Goat Milk and Milk Products in Dengue Fever. JPBMS. 2011;8(06):1-5.

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