Exploring ancient and modern medical learning A Publication of Himalaya Wellness Company Probe Vol LXII No. 3 • May–Aug 2023 Quarterly • ISSN 0970-3039 Liv.52 in the Management of Infective Hepatitis Septilin in the Management of Respiratory Tract Infections The Role of Growth Factors in Dengue and Thrombocytopenia The Role of Hormones in Female Pattern Hair Loss Vitamin Insufficiency and Health Outcomes in Children Liv.52 DS in the Management of Nonalcoholic Fatty Liver Disease Scan to read the e-version of Probe
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Probe • Vol LXII • No. 3 • May–Aug 2023 • i Editorial Dear Doctor, We are delighted to announce that 2023 marks a milestone year for some of Himalaya’s products—Bonnisan completes 50 years, and Evecare, Confido, and OphthaCare complete 25 years in their journey of bestowing wellness. Thank you for your continual support for Himalaya’s products, doctor! This issue of Probe brings to you yet another collection of interesting medical updates. The uncertainties associated with platelet levels during dengue fever can be life-threatening. Thrombocytopenia is thus considered a significant predictor of the clinical severity of dengue. Know more about the mechanisms involved in thrombocytopenia associated with dengue fever in the From Other Pages section. This section also features an article on how hormones, other than androgens, can trigger the development of female pattern hair loss. Excerpts from the preclinical and clinical trial reports that prove the efficacy of Liv.52 DS in the management of drug-induced liver injury and nonalcoholic steatohepatitis, Septilin in the management of respiratory tract infections, and Liv.52 in the management of infective hepatitis are featured in the Evidence-Based Insights section. An excerpt of a recently published clinical study that shows the effect of Liv.52 DS Tablets on various liver parameters in nonalcoholic fatty liver disease is featured in the Latest Research section. Besides, engaging articles about different vitamin deficiencies seen in children and the pharmacologic significance of the herbs Tinospora cordifolia, Terminalia arjuna, and Syzygium aromaticum are part of this issue. We hope you find this issue’s collection of articles informative. — Editor
Probe • Vol LXII • No. 3 • May–Aug 2023 • iii Contents Evidence-Based Insights Liv.52 DS . . . . . . . . . . . . . . . . . . . . . . . . . 2 Septilin . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Liv.52 . . . . . . . . . . . . . . . . . . . . . . . . . . 14 From Other Pages The Role of Growth Factors in Dengue and Thrombocytopenia . . . . . . . . . . . . . . . . . . . . 22 The Association Between Hormones and Female Pattern Hair Loss . . . . . . . . . . . . . . . . . .24 Review—Journal and Online . . . . . . . . . . . . . . . 26 Latest Research Efficacy of Liv.52 DS on Various Liver Parameters in Nonalcoholic Fatty Liver Disease: A Cumulative Analysis . . . .28 Drug Alert . . . . . . . . . . . . . . . . . . . . . . . . .30 Abstracts From Literature . . . . . . . . . . . . . . . . . 32 Upcoming Events . . . . . . . . . . . . . . . . . . . . . 40 Herbal Notes Tinospora cordifolia . . . . . . . . . . . . . . . . . . . . 42 Terminalia arjuna . . . . . . . . . . . . . . . . . . . . .43 Syzygium aromaticum . . . . . . . . . . . . . . . . . . . 44
iv • Probe •Vol LXII • No. 3 • May–Aug 2023 Editor: Dr Jayashree B Keshav Editorial Team: Shruthi VB, Shruthi VK, Harika GS, Shruthi M, Priyakshi M, Keerthini D, Harshitha C Layout Artists: Dayananda RS, Santosh G, Monesh NP For queries and other communications: The Editor—Probe Scientific Publications Division Himalaya Wellness Company Makali, Bengaluru 562162 Karnataka, India E-mail: publications@himalayawellness.com Copyright © 2023 Himalaya Wellness Company All content in this journal/publication is the property of Himalaya Wellness Company and is protected by Indian and international copyright laws. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance, of the content in this journal/publication, without written permission from the owner, is strictly prohibited. For permission to reproduce articles/information published in this journal/publication, please write to publications@himalayawellness.com Nutrition Update Insufficiency of Vitamins and Health Outcomes in Children……. 48 Prescribing Information Florasante (Capsule) . . . . . . . . . . . . . . . . . . . . 52 Cystone forte (Tablet) . . . . . . . . . . . . . . . . . . . 54 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56 Laughter, The Best Medicine Riddle Time Think Wise
Evidence-Based Insights
2 • Probe •Vol LXII • No. 3 • May–Aug 2023 Clinical Evidence 1 Liv.52® DS (SYRUP, TABLET) Liv.52 DS is a hepatospecific formulation, designed for the treatment and management of liver disorders. Liv.52 DS has a wide spectrum of therapeutic applications. Liv.52 DS restores the metabolic efficiency of the liver, minimizes damage to the hepatic parenchyma, and accelerates the rate of recovery in various liver disorders such as drug-induced hepatitis. In nonalcoholic steatohepatitis, Liv.52 DS decreases uptake of free fatty acids by hepatocytes, decreases DNA fragmentation through antioxidant activity, and increases urea and albumin secretion. Liv.52® DS in the Management of Statin-Induced Liver Injury Aim To evaluate the efficacy of Liv.52 DS tablet as a hepatoprotective agent in prophylaxis with statin therapy Materials and Methods This open, randomized, comparative, and prospective clinical trial enrolled 50 patients (40 male and 10 female patients; aged 18–70 y) on antihyperlipidemic therapy with statins. Patients with a history of extensive disease that requires hospitalization and pregnant women were excluded from the study. A written informed consent was obtained from all the patients who were included in the study. Patient history was noted, and a thorough clinical examination and symptomatic evaluation were performed. The patients were randomized into 2 groups of 25 each: Liv.52 DS tablet + atorvastatin group and atorvastatin-alone group. The patients were advised to take 1 Liv.52 DS tablet, BID, and 1 atorvastatin tablet (10 mg), BID, for 3 months, based on the groups they were assigned into. All the patients were reviewed every week till the end of the treatment period. The evaluation included clinical examination for general health, body temperature, liver size, skin health, and weight, and subjective signs such as coating of the tongue, loss of appetite, nausea and vomiting, and pain and discomfort in the right hypochondrium. The liver function tests, hemogram, and other biochemical tests were performed at the end of every month for 3 months. The clinical and laboratory evidence of the normal functioning of the liver was considered the primary end point. The changes in the levels of liver function parameters after the treatment were statistically analyzed using repeated measures ANOVA test followed by Dunnett’s multiple comparison post hoc test. The minimum level of significance was fixed at 95% confidence limit, and a 2-sided P value of < .05 was considered significant. Results All the patients completed the trial. At the end of 3 months, a significant increase (P < .01) in the mean values of serum glutamic pyruvic transaminase (SGPT) from 45.87 ± 4.98 to 102.70 ± 12.05 IU/L, serum glutamic oxaloacetic transaminase (SGOT) from 42.70 ± 4.74 to 98.87 ± 12.35 IU/L, and total bilirubin from 0.800 ± 0.026 to 1.022 ± 0.077 g/dL was observed in the atorvastatin-alone group. No such increase in SGPT, SGOT, and total bilirubin
Probe • Vol LXII • No. 3 • May–Aug 2023 • 3 Liv.52 DS in the Management of Statin-Induced Liver Injury levels was observed in the Liv.52 DS tablet + atorvastatin group, after 3 months (Figures 1–3). The differences between the groups in terms of physical examination parameters (such as the skin, general health, body temperature and weight, and liver size) and subjective signs (such as coating of the tongue, loss of appetite, nausea and vomiting, and pain and discomfort in the right hypochondrium) were insignificant. Likewise, no significant differences were noticed in the other biochemical and hematological parameters between the groups. Conclusion The results of this study show that in the atorvastatin-alone group, there was a significant increase in the mean values of SGPT, SGOT, and total bilirubin after 3 months, whereas no such increase in SGPT, SGOT, and total bilirubin was observed in the Liv.52 DS tablet + atorvastatin group, after 3 months of therapy. Also, there were no significant differences between the groups in terms of physical examination and subjective signs at the end of the treatment period. The hepatoprotective effect of Liv.52 DS tablet may be attributed to the synergistic action of its constituent herbs such as Capparis spinosa, Cichorium intybus, Solanum nigrum, Cassia occidentalis, Terminalia arjuna, Achillea millefolium, and Tamarix gallica. Thus, this study shows that Liv.52 DS tablet has hepatoprotective effect against statin-induced liver damage. Summary • Fifty patients (of both sexes) on antihyperlipidemic therapy with statins were included in the study. • The patients were randomized into 2 groups; Liv.52 DS tablet + atorvastatin tablet (1 tablet each, BID) group and atorvastatin-alone (1 tablet, BID) group, for 3 months. • Symptomatic evaluation, clinical examination, liver function tests, hemogram, and other biochemical tests were performed at monthly intervals for 3 months. • A significant increase in the mean values of SGPT, SGOT, and total bilirubin levels was observed in the atorvastatin-alone group, after 3 months. • No increase in the SGPT, SGOT, and total bilirubin levels was observed in the Liv.52 DS tablet + atorvastatin group, after 3 months. • The study results confirm the hepatoprotective effect of Liv.52 DS against statin-induced liver damage. Figure 1. A Comparison of the Increase in the SGPT Level in the Liv.52 DS + Atorvastatin and Atorvastatin-Alone Groups SGPT, serum glutamic pyruvic transaminase. 20 120 100 80 60 40 0 SGPT, IU/L a a Liv.52 DS + Atorvastatin Month 1 Month 2 Month 3 Atorvastatin alone aP < .01 compared with month-1 value Month 1 Month 2 Month 3 Figure 2. A Comparison of the Increase in the SGOT Level in the Liv.52 DS + Atorvastatin and Atorvastatin-Alone Groups SGOT, serum glutamic oxaloacetic transaminase. 20 120 100 80 60 40 0 SGOT, IU/L a a Liv.52 DS + Atorvastatin Month 1 Month 2 Month 3 Atorvastatin alone aP < .01 compared with month-1 value Figure 3. A Comparison of the Increase in the Total Bilirubin Level in the Liv.52 DS + Atorvastatin and Atorvastatin-Alone Groups 0.2 1.4 1.2 1.0 0.8 0.6 0.4 0 Total Bilirubin, g/dL a Liv.52 DS + Atorvastatin Atorvastatin alone aP < .01 compared with month-1 value
4 • Probe •Vol LXII • No. 3 • May–Aug 2023 Clinical Evidence 2 Liv.52® DS in the Management of Nonalcoholic Steatohepatitis Aim To evaluate the efficacy and safety of Liv.52 DS in the management of nonalcoholic steatohepatitis (NASH) Materials and Methods This open clinical study enrolled 50 patients (21 male and 29 female patients; mean age 48.28 ± 9.92 y) suffering from steatohepatitis, characterized by elevated liver enzyme levels and hepatomegaly with pain and discomfort in the right upper abdomen. Patients with severe metabolic disorders, carcinoma of the liver or the pancreas, preexisting systemic disease that requires long-term medications, genetic and endocrinal disorders, and pregnant and lactating women were excluded from the study. At the initial visit, a detailed family and medical history was collected from all the patients. A thorough systemic examination and hematological and biochemical tests including liver function tests, ultrasonography (USG), and a noninvasive nonalcoholic fatty liver disease (NAFLD) scoring were performed to grade the severity of liver fibrosis. The patients were instructed to take Liv.52 DS tablet at a dosage of 2 tablets, BID, for 3 months. All the adverse events, either reported or observed by the patients, were recorded as either unrelated, possible, or probable. All the patients were followed up at monthly intervals for 3 months. Clinical assessment scores were recorded using a 5-point scale on each visit as follows: 5, good improvement/no complaints; 4, considerable improvement; 3, improvement; 2, no change; 1, worsening. The USG findings were recorded using a scale of 0 to 3, where 0, no fatty liver; 1, mild fatty liver; 2, moderate fatty liver; 3, severe fatty liver. The NAFLD score was evaluated as follows: NAFLD score < − 1.455 = F0-F2; NAFLD score − 1.455 to 0.675 = indeterminate score; and NAFLD score > 0.675 = F3-F4. NAFLD fibrosis score was calculated using the following formula: − 1.675 + 0.037 × age (year) + 0.094 × BMI (kg/m2) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × aspartate aminotransferase/alanine aminotransferase ratio − 0.013 × platelet count (× 109/L) − 0.66 × albumin. The overall clinical efficacy was assessed using a 6-point scale as follows: 6, symptoms became worse; 5, no change; 4, slight improvement; 3, moderate improvement; 2, marked improvement; and 1, cured. Improvement in liver function parameters after the administration of Liv.52 DS tablet and the incidence of adverse events and overall compliance to the therapy were considered the predefined primary and secondary end points, respectively. Statistical analysis was performed using repeated measure of ANOVA followed by Friedman test and Dunn’s multiple comparisons test for between-thegroup analyses followed by the paired t test. Results Significant improvements in abdominal discomfort due to hepatomegaly, fatigue, weakness, body weight, and recurrent infections were observed at the first month, and further improvement was seen by the end of the treatment period (Table 1). After the treatment with Liv.52 DS tablet, gradual improvements in the hematological and biochemical parameters were observed at the end of the
Probe • Vol LXII • No. 3 • May–Aug 2023 • 5 Liv.52 DS in the Management of Nonalcoholic Steatohepatitis study period. Significant changes in the USG findings and NAFLD scores were also noticed (Tables 2 and 3). No adverse reactions were observed or reported during the study. Conclusion The results show that treating patients with NASH with Liv.52 DS tablet for 3 months improved their clinical and liver function parameters, USG findings, and NAFLD scores. Thus, Liv.52 DS tablet is effective and safe in the management of NASH. Summary • Fifty patients (of both sexes) suffering from steatohepatitis were enrolled into this study. • The patients were advised to take 2 Liv.52 DS tablets, BID, for 3 months. • Systemic examination, hematologic and liver function tests, ultrasonography (USG), and a noninvasive NAFLD scoring were performed at monthly intervals. • Improvements in liver function parameters after the administration of Liv.52 DS tablets and incidence of adverse events and overall compliance to the therapy were considered as the primary and the secondary end points, respectively. • Significant improvements in abdominal discomfort due to hepatomegaly, fatigue, weakness, body weight, and recurrent infections were observed. • Gradual improvements in the hematological and biochemical parameters were also observed. • Significant improvements in the USG findings and NAFLD scores were also noticed. • The study results confirm the safety and efficacy of Liv.52 DS tablet in the management of NASH. Sources: Das JKL, et al. Med Update. 2007;15(7):31–36. Ghosh S, et al. Int J Curr Res Aca Rev. 2014;2(9):1–12. Table 1. Effect of Liv.52 DS on Clinical Parameters Parameter Screening Month 1 Month 3 Abdominal Discomfort Due to Hepatomegaly 0.62 ± 0.67 2.38 ± 0.67a 4.62 ± 0.49a,b Fatigue 0.68 ± 1.52 2.62 ± 0.92a 4.74 ± 0.44a,b Weakness 0.44 ± 0.58 2.54 ± 0.54a 4.80 ± 0.40a,b Weight Loss 3.20 ± 2.42 3.96 ± 1.44 4.60 ± 0.61c Recurrent Infections 4.32 ± 1.17 4.76 ± 0.48 5.00 ± 0.00d Statistical test: Friedman test followed by Dunn’s multiple comparisons test. aP < .001; bP < .001; cP < .01; and dP < .05 compared with at-entry values. Table 2. Effect of Liv.52 DS Based on USG Findings (Mean ± SD) Before the Treatment After the Treatment Significance 1.58 ± 0.64 0.66 ± 0.56 P < .0001 USG, ultrasonography. Table 3. Effect of Liv.52 DS on NAFLD Score At Entry End of the Study − 0.98 ± 0.39 − 1.22 ± 0.41 NAFLD score interpretation: < − 1.455 = F0-F2; − 1.455 to 0.675 = indeterminate score; and > 0.675 = F3-F4. NAFLD, nonalcoholic fatty liver disease.
One of the world’s most enduring phytomedicines, with Double Strength protection… Liv.52® DS Unparalleled in liver care In the management of: ( S Y R U P , T A B L E T ) NAFLD and NASH Drug-induced hepatitis Jaundice and anorexia during pregnancy Dosage NAFLD and NASH: 1–2 tablets twice daily. Drug-induced hepatitis: 1–2 teaspoonsful/tablets twice daily with anti-TB/statin treatment. Jaundice and anorexia during pregnancy: 1 teaspoonful/tablet twice daily for 8 weeks. ® Regd. Trademark Liv.52 DS Unparalleled in liver care
Probe • Vol LXII • No. 3 • May–Aug 2023 • 7 Preclinical Evidence Septilin® (SYRUP, TABLET) Septilin is recommended for the treatment and management of various infections and to prevent their recurrence. Septilin augments host response, reduces inflammation, and corrects the underlying pathologic features associated with recurrent infections. When co-prescribed with antibiotics, Septilin ensures faster recovery and prevents recurrence. Septilin is a valuable adjuvant in infection management and provides excellent short-term and long-term safety. Immunotherapeutic Modification by Septilin Aim To evaluate the effect of Septilin on both nonspecific and specific defense mechanisms in experimental rat and mice models Materials and Methods The study included Swiss albino mice and wistar rats for different study methods. Escherichia coli–induced abdominal sepsis in mice This method was carried out in 2 parts. The first part involved subculturing the pathogenic strain of E coli in the nutrient broth at 37°C and 50 rpm for 18 to 24 hours. The vitality of culture was determined using repeated dilution and surface spreading methods. The total viable cell count on the MacConkey agar plates was determined after a 24-hour incubation period. The ability of E coli to cause 100% mortality for up to 48 hours was tested. In the second part, 33 Swiss albino mice (weighing between 25 and 35 g) were divided into 2 groups: group 1 (control, n = 18) received tap water, and group 2 (n = 15) received Septilin syrup at a dose of 20 mL/kg body weight. Blood was collected for total and differential leukocyte counts. E coli (5 × 108) cells were injected intraperitoneally into mice in both the groups, and percentage mortality was observed after 24 hours. Bactericidal activity of polymorphonuclear cells in rats This was an in vitro method, in which the subcultured E coli was washed 3 times, a known volume of phosphate buffered saline was suspended, and the turbidity of the suspension was measured spectrophotometrically at 540 nm. The required viable E coli cells (1.6 × 107) were determined. A total of 28 wistar rats were divided into 2 groups: group 1 (control, n = 16) received water at a dose of 10 mL/kg body weight, and group 2 (n = 12) received Septilin syrup at a dose of 10 mL/kg body weight orally, once daily, for 15 days. Venous blood (8 mL) was collected. Staphylococcus aureus–induced sepsis in neutropenic mice This method included 27 albino mice and were randomized into 2 groups: group 1 (n = 15) received water at a dose of 20 mL/kg body weight, and group 2 (n = 12) received Septilin syrup at a dose of 20 mL/kg body weight, once daily, orally for 15 days. Carbon clearance assay in mice Swiss albino mice (n = 15) were divided into 2 groups: group 1 (n = 9) received 10 mL/kg body weight of tap water, and group 2 (n = 6) received 10 mL/kg body weight of Septilin syrup, orally, once daily, for 15 days. On day 15, both the groups were
8 • Probe •Vol LXII • No. 3 • May–Aug 2023 Immunotherapeutic Modification by Septilin intravenously administered 0.1 mL of colloidal carbon after a warm-up period of 15 to 20 min at 37°C. One drop of blood was collected at 2, 5, 10, 15, 20, 20, 30, 45, 60, and 90 min by tail nipping. The graph of absorbance against time was plotted, and the area under curve determined. Humoral response in normal and immune-deficient rats In this method, wistar rats (n = 106) were divided into 4 groups: group 1 rats (n = 35) received water (10 mL/kg body weight), once daily, orally from day (- 9) to day (+ 4). Group 2 (n = 26) rats received 10 mL/kg body weight of water, once daily, orally from day (- 9) to day (+ 4), and on day (+ 2), 400 mg/kg body weight of cyclophosphamide was administered orally in addition to water treatment. Group 3 rats (n = 36) received Septilin syrup at a dose of 3 g/kg body weight, once daily, orally from day (- 9) to day (+ 4), and on day (+ 2), 400 mg/kg body weight of cyclophosphamide was administered orally in addition to Septilin treatment. All parameters were statistically analyzed either by the unpaired Student’s t test or the c2 test. Results Effect of Septilin on E coli–induced abdominal sepsis There was no mortality in the group treated with Septilin compared with 77.8% mortality in the control group 24 hours after receiving E coli cells (Figure 1). After 15 days of treatment with Septilin, total leukocyte, absolute lymphocyte, and absolute neutrophil counts significantly increased compared with that in the control group (Figure 2). Effect of Septilin on bactericidal activity of polymorphonuclear cells The total number of viable E coli cells (× 106/mL) in the Septilin-treated group (1.36 ± 0.39) was significantly lower compared with that in the control group (3.50 ± 0.77). The absolute neutrophil count (× 103/mL) in the Septilin-treated group (1786.00 ± 163.66) was significantly more than that in the control group (1243.50 ± 155.53). Figure 1. Effect of Septilin on Mortality in Escherichia coli– Induced Abdominal Sepsis Figure 2. Effect of Septilin Treatment on Leukocyte Counts a,b,cP < .001. Continued on page 12… 20 40 60 24 h 48 h 80 No mortality in the Septilin Rx group Control Septilin 100 0 Mortality, % 3000 2250 1500 750 a b a b c c 3750 4500 Total WBC Absolute Neutrophil Absolute Lymphocyte 5250 6000 Control (n = 15) Septilin (n = 15) 6750 0 Count (x 103/mL)
Probe • Vol LXII • No. 3 • May–Aug 2023 • 9 Clinical Evidence 1 Efficacy and Safety of Septilin® Tablet in the Management of Respiratory Tract Infections Aim To evaluate the safety and efficacy of Septilin tablet in the management of upper and lower respiratory tract infections Materials and Methods This open clinical evaluation included 148 patients who attended the OPD of Bangalore Medical College (Bengaluru, Karnataka, India). Inclusion criteria In this study, adult patients of either sex, aged between 18 and 50 years, with upper and lower respiratory tract infections were included. Exclusion criteria Patients with severe psychiatric/cardiac, metabolic, gastrointestinal, or metabolic disorders; severe infections such as pneumonia, tuberculosis, status asthmaticus, and severe bronchospasm; and pregnant and lactating patients were excluded. Study procedure The number of patients with respiratory tract infections and the duration of illness are given in Table 1. Of the 148 patients with respiratory tract infections, 112 patients had upper respiratory tract infections (URTIs) such as tonsillitis, pharyngitis, rhinitis, laryngitis, and sinusitis, and 36 patients had lower respiratory tract infection (LRTI), that is bronchitis. All patients were physically examined; their ear, nose, throat, and chest were thoroughly examined; and their vitals, including respiratory rate, were recorded in case report forms. The patients were prescribed Septilin tablets at a dosage of 2 tablets, BID, for 6 weeks and were followed up at the end of the second, fourth, and sixth weeks for analyzing the presence of symptoms. The primary end points were clinical recovery from symptoms of URTIs and LRTIs, and the secondary end points were clinical safety and toxicity profile of Septilin tablet. Statistical analysis The study results were evaluated statistically using the Fisher’s exact test for the presence or absence of various signs and symptoms. Results The control of symptoms and gradual improvement in response to the treatment were noticed after 2 weeks, and further improvement was observed Table 2. Effect of Septilin Tablet on Respiratory Tract Infections Parameter At Entry Week 2 Week 4 Week 6 Tonsillitis 28 17 8a 3 Pharyngitis 24 8a 2b 0 Laryngitis 8 0 0 0 Sinusitis 20 12 7a 2b Rhinitis 32 2b 0 0 Bronchitis 36 20 11a 4b aP < .01 compared with at-entry values. bP < .001 compared with at-entry values. Table 1. The Number of Patients With Respiratory Tract Infections and the Duration of Illness Indication Patients, n Duration of Illness, d Respiratory Tract Infections 148 — Upper respiratory tract infections 112 — Tonsillitis 28 5.26 ± 2.5 Pharyngitis 24 7.23 ± 4.4 Laryngitis 8 7.58 ± 5.1 Sinusitis 20 5.3 ± 1.26 Rhinitis 32 7.47 ± 3.22 Lower respiratory tract infections 36 — Bronchitis 36 9.42 ± 3.41
10 • Probe •Vol LXII • No. 3 • May–Aug 2023 with continued treatment (Table 2). In URTIs, of the 28 patients with tonsillitis, only 17, 8, and 3 patients had tonsillitis by the end of the second, fourth, and sixth weeks, respectively. Among the 24 patients with pharyngitis, only 8 and 2 patients had pharyngitis by the end of the second and fourth weeks; and by the end of 6 weeks, none of the patients had the condition. Patients with sinusitis were advised steam inhalation along with Septilin therapy. Of the 20 patients with sinusitis, only 12, 7, and 2 patients had sinusitis by the end of the second, fourth, and sixth weeks, respectively. Patients with rhinitis (n = 31) were also advised steam inhalation along with Septilin therapy. The symptoms reduced significantly by 2 weeks, and all the patients responded well by 4 weeks. In patients with LRTIs, 36 of them presented with bronchitis; of which only 20, 11, and 4 had the symptoms by the end of the second, fourth, and sixth weeks, respectively. Of the 148 patients treated, only 2 patients experienced mild abdominal discomfort, and all the patients tolerated the drug well. None of the patients were withdrawn from the study due to adverse effects. Discussion Septilin is a polyherbal preparation, and the effect of the formulation is due to the synergistic action of the ingredients. The principal herbs present in Septilin include Tinospora cordifolia, Emblica officinalis, Glycyrrhiza glabra, Moringa pterygosperma, Balsamodendron mukul, and Rubia cordifolia. T cordifolia has potent immunomodulatory and immunostimulatory properties, which increase the levels of antibodies and activate macrophages. It also improves phagocytic and intracellular bactericidal capacities of neutrophils. E officinalis enhances cell survival and increases phagocytosis and IFN-γ production. Glycyrrhizin from G glabra potentiates the reticuloendothelial system, enhances immunostimulation, and acts on macrophage function in vitro, leading to stimulation of macrophages de novo. β-Glycyrrhetinic acid from G glabra is a potent inhibitor of the classical complement pathway. E officinalis has antibacterial property, especially against Escherichia coli, Klebsiella pneumoniae, Klebsiella ozaenae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Salmonella paratyphi A and B, and Serratia marcescens. B mukul has strong anti-inflammatory potential. R cordifolia has antibacterial property. M pterygosperma possesses antibacterial and antiviral properties and inhibits the growth of gram- positive and gram-negative bacteria such as E coli, S typhi, and S paratyphi. T cordifolia and E officinalis possess antipyretic property. Conclusion The study revealed that Septilin tablets significantly alleviated the symptoms of URTIs and LRTIs, and Septilin was safe and well tolerated in patients at the dose administered. Summary • This study included 148 patients with URTIs and LRTIs. • All patients were prescribed Septilin tablet at a dosage of 2 tablets, BID, for 6 weeks. • The symptoms were reduced, and gradual improvement in response to the treatment was noticed after 2 weeks. Further improvement was observed with continued treatment. • No adverse effects were observed in patients treated with Septilin. Efficacy and Safety of Septilin Tablet in the Management of Respiratory Tract Infections
Probe • Vol LXII • No. 3 • May–Aug 2023 • 11 Clinical Evidence 2 Effect of Septilin® Syrup on Recurrent Upper Respiratory Tract Infections in Children Aim To determine the efficacy of Septilin syrup in the management of recurrent upper respiratory tract infections (URTIs) in children Materials and Methods This trial included 20 children (9 mo to 5 y of age) with upper respiratory tract infections (URTIs) from the pediatric OPD of Goa Medical College Hospital (Goa, India). Infants and children with recurrent URTIs of suspected viral etiology were included. All patients underwent routine blood counts, throat cultures, and a chest X-ray. Septilin syrup was prescribed at an initial dose of 1 teaspoon, BID, for infants and 2 teaspoons, BID, for children. Subsequently, the dose was increased to 1 teaspoon, TID, for infants and 2 teaspoons, TID, in those children who did not show a significant improvement; and in most patients, Septilin was administered for 12 to 16 weeks. The weight gain and regression of signs and symptoms were evaluated at the follow-up visit. The responses were graded as 3 categories: • Excellent, in case children had complete cessation of symptoms during and after Septilin syrup therapy and remained asymptomatic over the next 3 months. • Good, in case children had complete cessation of symptoms during and after the therapy but became symptomatic during the next 3 months. • Poor, in case children had recurrent or persistent symptoms during and after the completion of the therapy. Results The frequency of URTI recurrence was 4 times, in each child, prior to Septilin therapy. Ten patients (50%) who were younger than 2 years showed an excellent response, while the other 10 patients (50%) displayed good response. The latter group included 5 patients aged 3 to 5 years and 5 patients under the age of 3 years. The dose of the medication had to be increased, and the duration of the treatment increased to 8 to 12 weeks. The avoidance of antibiotics was possible in 75% of cases, and the remaining 25% required antibiotics. As the study included patients with a highly suspected viral etiology, none of the patients could be categorized as being in the poor response group. No side effects were observed. All the parents expressed satisfaction in terms of the acceptability and palatability of Septilin syrup. At follow-up, a majority of the patients reported improved symptoms, and all the patients reported good appetite and weight gain. Conclusion The study demonstrated that Septilin syrup is effective in the management of recurrent URTIs. In addition, Septilin syrup increased appetite and weight gain. Therefore, Septilin syrup may be effective in treating recurring viral URTIs. Summary • The study included 20 children with an age range from 9 months to 5 years with upper respiratory tract infections. • The patients were prescribed Septilin syrup at an initial dose of 1 teaspoon, BID, for infants and 2 teaspoons, BID, for children. Subsequently, the
12 • Probe •Vol LXII • No. 3 • May–Aug 2023 dose was increased to 1 teaspoon, TID, for infants and 2 teaspoons, TID, for children. The treatment was administered for 12 to 16 weeks. • After the treatment with Septilin syrup, 50% of the patients showed an excellent response and remaining 50% showed good response. • After prescribing Septilin syrup, the avoidance of antibiotics was possible in 75% of cases, and the remaining 25% were given antibiotics. • No side effects were observed in patients treated with Septilin syrup. • At follow-up, majority of the patients reported improved symptoms, and all patients reported good appetite and weight gain. Sources: Rao CS, et al. Indian J Exp Bio. 1994;32:553–558. Rajarathna K, et al. Med Update. 2010;18(8):23–27. Gaunekar L, et al. Antiseptic. 1988;4:250–251. Effect of Septilin on S aureus–induced sepsis S aureus was administered intravenously for 24 hours. There was a 66.6% mortality in the control group (n = 15), while 20% mortality (n = 12) in the Septilin-treated group. After 48, 72, 96, and 120 hours, no more mortality was noted. Effect of Septilin on carbon clearance The total area under the time–absorbency curve in the Septilin-treated group was 10.06 ± 0.71 and 15.46 ± 1.78 in the control group. Effect of Septilin on humoral response in normal and immunedeficient rats Septilin increased the titer of anti-SRBC hemagglutination antibodies in normal rats by 5.7 fold and showed remarkable resistance to cyclophosphamide-induced humoral suppression. This suggests a significant potentiating action of Septilin on humoral immunity. Conclusion The results of the study suggest that Septilin treatment increased the number of neutrophils in mice, increased the bactericidal activity of neutrophils in rats, accelerated the elimination of colloidal carbon, and prevented mortality from E coli–induced abdominal sepsis in mice. Septilin treatment reduced bacteremia after injecting S aureus in neutropenic mice, potentiated humoral immunity in rats, and counteracted cyclophosphamide-induced humoral suppression in rats. Summary • This study included Swiss albino mice and wistar rats for different study methods, and they were treated with Septilin syrup at a dosage of 20 mL/kg body weight, once daily, orally for 15 days. • Septilin-treated rats showed a 5.7-fold rise in anti-SRBC hemagglutination antibody titer mediated by IgG and IgM. • Septilin showed a potentiating effect on humoral immunity. ...Continued from page 8 (Immunotherapeutic Modification by Septilin) Effect of Septilin Syrup on Recurrent Upper Respiratory Tract Infections in Children
Septilin® Builds the body’s own defense mechanism Manage recurrent respiratory infections with… Septilin Builds the body’s own defense mechanism ® Regd. Trademark ( SYRUP, TABLET ) • Corrects the underlying pathological features of infections and allergies • Offers beneficial antimicrobial and antiviral actions • Improves the body’s immune defenses Indications • Recurrent RT and ENT infections (tonsillitis, pharyngitis, bronchitis, sinusitis, and otitis media) • Resistance to antibiotic therapy • As an adjuvant to anti-infective therapy Duration of Therapy: Minimum 4 weeks Dosage Syrup: Children: 1–2 teaspoonsful (5–10 ml) thrice daily. Adults: 2 teaspoonsful (10 ml) thrice daily. Tablet: Children: 1 tablet twice daily. Adults: 2 tablets twice daily till the symptoms are relieved, followed by 1 tablet twice daily as maintenance therapy.
14 • Probe •Vol LXII • No. 3 • May–Aug 2023 Preclinical Evidence Liv.52® (SYRUP, TABLET) Liv.52 is a hepatospecific formulation, designed for the treatment and management of liver disorders. Liv.52 has a wide spectrum of therapeutic applications. Liv.52 restores the metabolic efficiency of the liver, minimizes damage to the hepatic parenchyma, and accelerates the rate of recovery in various liver disorders such as infectious hepatitis and alcoholic liver diseases. Liv.52 is a valuable adjuvant during prolonged illness. In anorexia, Liv.52 improves appetite, digestion, and assimilation. Effect of Liv.52® on Hepatic Enzymes Aim To examine the effect of Liv.52 and the extract of Solanum nigrum on the growth rate of rats; hepatic mitochondrial, microsomal, and lysosomal enzymes; and hexobarbital sleeping time, and also to investigate whether Liv.52 offers any protection against the hepatotoxicity of carbon tetrachloride (CCl4) Materials and Methods The S nigrum extract was prepared by homogenizing 100 g of S nigrum leaves in distilled water (10% homogenate, w/v). It was kept at 80°C for 1 hour and centrifuged. The clear supernatant was then concentrated to dryness in vacuo. Male weanling rats (Druckrey strain) were divided into 3 groups: group 1 received Liv.52 (0.125 mL/kg body weight/d), group 2 received the S nigrum leaf extract (equivalent to its corresponding amount in Liv.52), and group 3 (control) received normal saline for 11 weeks. All the rats had free access to a standard pellet diet and water, and 2 rats were housed in one cage. Their body weight was recorded every week. To measure the hexobarbital sleeping time, the animals were intraperitoneally administered 125 mg of sodium hexobarbital per kg of body weight. Sleeping time was recorded as the time between losing and restoring the righting reflex. Six rats each from the control and Liv.52 groups received a sublethal dose of CCl4 (0.7 mL/kg body weight) intraperitoneally for 2 days. All animals were then fasted for 24 hours and were killed after 48 hours by decapitation. The livers were immediately removed and rinsed with cooled normal saline, and 10% homogenate (w/v) in 0.25 M sucrose was prepared. DNA was extracted from a 2-mL aliquot of the homogenates using the Schneider method and was estimated using diphenylamine reaction. Results Liv.52-fed rats showed significantly better growth at the initial phase (weeks 3–8) compared with those administered the extract of S nigrum or controls; however, by the final phases (weeks 8–11), the body weights of rats in all groups were almost the same. The liver weight in all 3 groups was the same, but the liver protein level in the Liv.52-treated rats increased compared with the S nigrum–treated rats or control rats (Figure). According to DNA estimations, it was evident that there was no liver shrinkage (2.95 and 2.90 mg DNA/g of the liver in control rats and Liv.52-fed rats, respectively). The hexobarbital sleeping time reduced in the Liv.52-treated group (42 ± 6 min) compared with the control and S nigrum–fed group (63 ± 8 and 59 ± 4 min, respectively). The S nigrum–fed rats and Liv.52-treated rats had higher levels of succinate dehydrogenase, cytochrome c
Probe • Vol LXII • No. 3 • May–Aug 2023 • 15 of increase in these enzyme levels was more in S nigrum–fed rats than in Liv.52-treated rats. The activity of these enzymes was decreased in the control rats and Liv.52-treated rats that were administered CCl4. Upon the administration of CCl4 to the control and Liv.52-treated rats, the levels of the enzymes succinate dehydrogenase, cytochrome c oxidase, and ATPase were significantly reduced. In the control rats that were administered CCl4, the percentages of inactivation of aniline hydroxylase and aminopyrine N-demethylase were 73% and 70%, respectively, while the percentages of corresponding inactivation of these enzymes in Liv.52 + CCl4–administered rats were 45% and 69%, respectively. This shows that Liv.52 provides a certain amount of protection to microsomal aniline hydroxylase in CCl4-induced hepatotoxicity. The activity of hepatic lysosomal enzymes—acid phosphatase, alkaline phosphatase, acid deoxyribonuclease, acid ribonuclease, and cathepsin B—was decreased in Liv.52-treated rats compared with that in the control and S nigrum–fed rats. Table. Effect of Liv.52 and Solanum nigrum Leaf Extract on Hepatic Mitochondrial, Microsomal, and Lysosomal Enzyme Levels Enzymes*, (Units/g liver) Control Liv.52 S nigrum Untreated Untreated CCl 4 treated Untreated CCl4 treated Succinate Dehydrogenasea 17.7 ± 1.4 3.83 ± 1.4 21.9 ± 0.7 18.76 ±0.7 23.4 ± 1.1 Cytochrome c Oxidaseb 0.43 ± 0.07 0.298 ± 0.01 0.65 ± 0.08 0.415 ± 0.007 0.75 ± 0.13 Total ATPasec 6.37 ± 0.43 3.51 ± 0.3 Microsomal 8.69 ± 0.97 6.62 ±0.03 11.05 ± 0.36 Aniline Hydroxylased (× 102) 8.3 ± 0.9 2.28 ± 0.84 – 73# 12.8 ± 1.3 6.01 ±0.91 – 45# 6.7 ± 0.8 Aminopyrine N-Demethylasee 185 ± 10 55 ± 7.9 – 70# 475 ± 50 145 ± 21 – 69# 915 ± 10 Glucose-6-Phosphatasec 5.56 ± 0.24 4.19 ± 0.22 Lysosomal 5.58 ± 0.37 4.15 ± 0.18 Not done Acid Phosphatasef 21.2 ± 2.17 34.53 ± 4.7 + 63# 16.65 ± 0.77 28.9 ± 1.47 + 81# 23.5 ± 1.9 Alkaline Phosphatasef 7.22 ± 0.56 13.45 ± 2.29 + 88# 5.62 ± 0.53 10.18 ± 1.9 + 81# Not done Acid Deoxyribonucleaseg (× 10−3) 0.60 ± 0.1 Not done 0.37 ± 0.04 Not done 0.60 ± 0.03 Acid Ribonucleaseg (× 10−3) 2.67 ± 0.34 6.42 ± 1.6 + 140# 1.91 ± 0.1 4.72 ± 1.61 + 146 # Not done Cathepsin Bh 2.86 ± 0.12 2.33 ± 0.104 – 18# 1.86 ± 0.11 1.68 ± 0.08 – 9# 2.71 ± 0.34 *One enzyme unit is expressed as aµmole potassium ferricyanide reduced/min; b2.303 log OD min/OD min × conc. of cytochrome c; cµmole Pi liberated/min; dpmole p-aminophenol formed/min; enmol formaldehyde formed/min; fµmole phenol liberated/min; gOD/min; hµmole of tyrosine released/min. #Values indicate percentage increase (+) or decrease (–) in activity. Figure. Effect of Liv.52 and S nigrum Leaf Extract on the Growth Rate of Rats oxidase, and adenosine triphosphatase (ATPase) in the hepatic mitochondrial fraction (Table) compared with the control group rats. However, the magnitude Continued on page 19... Effect of Liv.52 on Hepatic Enzymes 120 130 140 150 160 170 180 190 200 210 100 80 50 40 60 Age, d 70 90 Liv.52 Control Solanumnigrum 110 0 0 10 20 30 40 50 60 70 BodyWeight, g
16 • Probe •Vol LXII • No. 3 • May–Aug 2023 Clinical Evidence 1 Efficacy of Liv.52® in the Management of Infective Hepatitis, Chronic Active Hepatitis, and Cirrhosis Aim To assess the efficacy of Liv.52 in the management of various liver diseases such as acute infective (viral) hepatitis, chronic active hepatitis, and cirrhosis Materials and Methods This controlled study included 104 patients, of whom 73 patients were treated with Liv.52 (at a dosage of 4 tablets, TID) and 31 patients served as controls. The number of patients in each category is presented in the Table. Table. Categories of Liver Diseases Type of Liver Disease Liv.52 Group, n Control Group, n Infective Hepatitis (Group A) 30 15 Chronic Active Hepatitis (Group B) 24 8 Cirrhosis (Group C) 19 8 The patients were analyzed for clinical parameters and improvements in the biochemical profile, liver function parameters, and histopathologic findings after a follow-up of 3 years. The results were graded as “good”, “fair”, and “poor” upon analysis of the data after the full study. Results Group A: infective hepatitis Clinical improvement Symptoms such as fever, anorexia, nausea, weakness, bone ache, headache, sleeplessness, flatulence, and epigastric discomfort were alleviated sooner in the Liv.52 group than in the control group. Biochemical profile (liver function tests) • Serum bilirubin: In the Liv.52 group, the serum bilirubin level reduced in most patients, within 7 days of treatment. Moreover, the level became normal or near normal in 73.33% of the patients within 2 to 3 weeks of the treatment. The trend of the changes in the serum bilirubin level is shown in the Figure. • Alkaline phosphatase (ALP): The level of ALP decreased faster in most patients (73.33%) in the Liv.52 group than in the control group (26.66%). • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT): In the Liv.52 group, 22 patients (73.33%) showed early improvement (within 2–3 wk), whereas 26.66% of the patients in the control group showed the same response within the same time frame. • Serum albumin: The serum albumin level significantly increased earlier in most patients in the Liv.52 group compared with that in the control group. Group B: chronic active hepatitis Clinical improvement Most patients in the Liv.52 group experienced alleviation in symptoms such as fever, anorexia, yellow Figure. Effect of Liv.52 on Serum Bilirubin Level in Infective Hepatitis 7 5 2 1 3 4 6 8 0 0 1 2 3 4 5 6 Week mg/100 mL Liv.52 Group Control Group
Probe • Vol LXII • No. 3 • May–Aug 2023 • 17 urine, flatulence, dyspepsia, jaundice, and weight loss compared with those in the control group. Biochemical profile • Serum bilirubin: In 9 patients in the Liv.52 group, the serum bilirubin level reduced and returned to normal in 6 months, whereas no improvement was observed in the control group within that time frame. • ALP: In 9 patients in the Liv.52 group, the ALP level improved and returned to normal in 6 months, whereas no such improvement was observed in the control group within that period. • SGOT and SGPT: In the Liv.52 group, SGOT and SGPT levels decreased in 21 patients (87.5%) in 12 months, whereas there was only a slight improvement in the control group during the same time. Group C: liver cirrhosis Clinical improvement Most patients in the Liv.52 group experienced alleviation in the signs and symptoms of cirrhosis compared with those in the control group. Biochemical profile • Serum bilirubin: In the Liv.52 group, the serum bilirubin level returned to normal in 13 patients in 12 months. • APL: In the Liv.52 group, the ALP level became normal in 4 patients in 9 to 12 months, and in 10 patients it became normal within 18 to 24 months. • Serum albumin/globulin: In the Liv.52 group, the serum albumin level became normal in 4 patients in 12 months and in 10 patients in 18 to 24 months. In the Liv.52 group, the serum globulin level became normal in 4 patients in 12 months and in 10 patients in 18 to 24 months. The results after the entire study were as follows: Infective hepatitis: The results were graded as good, fair, and poor in 73.33%, 23.33%, and 3.33% of the patients, respectively, in the Liv.52 group, and 26.66%, 66.66%, and 6.66% of the patients, respectively, in the control group. Chronic active hepatitis: The results were graded as good, fair, and poor in 37.50%, 50.00%, and 12.50% of the patients, respectively, in the Liv.52 group, and 0%, 50%, and 50% of the patients, respectively, in the control group. Liver cirrhosis: The results were graded as good, fair, and poor in 21.05%, 52.63%, and 26.32% of the patients, respectively, in the Liv.52 group, and 0%, 37.5%, and 62.5% of the patients, respectively, in the control group. No adverse effects were reported in the patients treated with Liv.52. Thus, Liv.52 was considered safe. Conclusion The treatment with Liv.52 appeared to be highly promising in patients with liver diseases such as liver cirrhosis, chronic active hepatitis, and infective hepatitis. Summary • In this study, a total of 104 patients were included, of whom 73 patients were treated with Liv.52, and 31 patients constituted the control group; the liver diseases studied were liver cirrhosis, chronic active hepatitis, and infective hepatitis. • The clinical improvement in symptoms was quicker in the Liv.52 group compared with that in the control group. • Among the patients with infective hepatitis treated with Liv.52, the results were graded as good, fair, and poor in 73.33%, 23.33%, and 3.33% of the patients, respectively. • Among the patients with chronic active hepatitis treated with Liv.52, the results were considered good, fair, and poor in 37.50%, 50.00% and 12.50% of the patients, respectively. • Among the patients with liver cirrhosis treated with Liv.52, the results were graded as good, fair, and poor in 21.05%, 52.63%, and 26.32% of the patients, respectively. • Liv.52 was found to be safe and effective in the treatment of liver diseases. Efficacy of Liv.52 in the Management of Infective Hepatitis, Chronic Active Hepatitis, and Cirrhosis
18 • Probe •Vol LXII • No. 3 • May–Aug 2023 Clinical Evidence 2 Efficacy of Liv.52® in the Management of Infective Hepatitis Aim To evaluate the efficacy of Liv.52 in the treatment of infective hepatitis Materials and Methods This controlled study included 50 patients (aged 15–65 y) with infective hepatitis, admitted to Darbhanga Medical College Hospital (Darbhanga, Bihar, India). The patients were equally divided into 2 groups: the treatment group received Liv.52 (6 tablets in divided doses) along with vitamin B complex and corticosteroids, daily, and the control group received vitamin B complex and corticosteroids only. All the patients underwent clinical examination, laboratory tests for total and differential white blood cell count, and stool and urine analyses. To assess the derangement in the liver function, specific tests such as estimations of serum bilirubin, alkaline phosphatase (ALP), thymol turbidity, serum glutamic pyruvic transaminase (SGPT), and serum glutamic oxaloacetic transaminase (SGOT) were carried out initially. These tests were repeated after 4 and 8 weeks of treatment to assess the degree of improvement in both the groups. Results The symptoms of infective hepatitis subsided substantially faster in the Liv.52 group than that in the control group—about half to two-thirds of the time taken in the control group (Figure 1). Liver function tests Serum bilirubin: The serum bilirubin level ranged from 5 to 22 mg% (average 12.8 mg%) in the Liv.52 group, and 5 to 18 mg% (average 12.06 mg%) in the control group. The serum bilirubin level decreased to 4.81 and 1.8 mg% in the control and Liv.52 groups, Figure 1. A Comparison of the Effect of the Respective Treatments on the Symptoms of Infective Hepatitis Figure 2. Effect of Liv.52 on Liver Function Parameters respectively, after 8 weeks of treatment (Table). In the Liv.52 group, the percentage reduction was 61% after 4 weeks and 86% after 8 weeks of treatment (Figure 2). Serum ALP: In the Liv.52 group, the serum ALP values were 14.72 and 11.08 KA units after 4 and 8 weeks of the treatment, respectively, which indicate reduction of 23% and 42%, respectively, compared with the initial values. Thymol turbidity: In the Liv.52 group, the average values were 6.8 and 3.64 units after 4 and 8 weeks, respectively, whereas in the control group, the values were 8.4 and 6 units, respectively (Figure 2). After 4 B: Before Treatment A: After Treatment Liv.52 Control (B) 25 (B) 25 (B) 22 (B) 22 (B) 23 (B) 23 (B) 25 (A) 12 (A) 15 (A) 6 (A) 10 (A) 10 25 25 (A) 4 (A) 9 (A) 6 (B) 20 Jaundice Loss of Appetite Loss of Weight Epigastric Discomfort Total No. of Cases 21 20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 Initial Initial Initial 4 wk 4 wk 4 wk 8 wk 8 wk 8 wk Serum Alkaline Phosphatase Values Thymol Turbidity Values Liv.52 Control
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