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Neuropathy is the most common disorder comprising peripheral nerve damage in diabetic patients. Prolonged hyperglycaemia and oxidative stress cause metabolic imbalance and are the key reasons for the development of diabetic neuropathy. Daidzein, a soy isoflavone possesses potent anti-hyperglycaemic and antioxidant activity. The present study aims to check the protective effect of Daidzein in diabetic neuropathy in rats. The experimental animal model involved induction of diabetes in rats by intraperitoneal injection of streptozotocin (55 mg/kg). Following confirmation of diabetes, the diabetic rats were subjected to oral treatment with varying doses of Daidzein (25, 50, and 100 mg/kg) and pregabalin (30 mg/kg) for a duration of 4 weeks, initiated 6 weeks after diabetes induction. Results indicated that Daidzein treatment led to a significant reduction in plasma glucose levels and an improvement in body weight among diabetic animals. Moreover, Daidzein demonstrated a positive impact on sensory functions, as evidenced by the effect on tail withdrawal and response latency. Mechanical hyperalgesia and allodynia, common symptoms of diabetic neuropathy, were also significantly reduced with both Daidzein and pregabalin treatment. Notably, nerve conduction velocities exhibited improvement following the administration of Daidzein and pregabalin. Further investigation into the molecular mechanisms revealed that Daidzein treatment resulted in a notable enhancement of antioxidant enzyme levels and a reduction in the overexpression of NOX-4 in the sciatic nerve. This suggests that Daidzein’s therapeutic effect is associated with the inhibition of oxidative stress via NOX-4. In summary, the findings of study suggests that, Daidzein treatment significantly attenuated diabetic neuropathy by inhibiting oxidative stress via NOX-4 inhibition.

Alzheimer’s disease is a progressive neurodegenerative condition. It is one of the most common 28 forms of dementia accounting for 60–80% of people suffering from dementia. There are very few medications that are approved for the treatment of Alzheimer’s disease. Baicalein, belonging to the flavone subclass of flavonoids, has been reported to have a neuroprotective effect by reducing oxidative stress and neuroinflammation, inhibiting the AChE enzyme, and reducing amyloid protein aggregation and toxicity. Memantine is one of the most important drugs used for treating Alzheimer’s disease. The purpose of this work was to study the effect of baicalein with memantine on aluminum chloride-induced neurotoxicity in Wistar rats. Aluminum chloride (100 mg/kg p.o.) was administered for 42 days in male Wistar rats to induce neurotoxicity. Baicalein alone (10 mg/kg) and a combination of baicalein (5 mg/kg and 10 mg/kg) with memantine (20 mg/kg) were administered for 42 days. Treatment of baicalein with memantine showed significant improvement in behavioral parameters. The combination reduced oxidative stress and the formation of β-Amyloid plaques and increased brain-derived neurotrophic factor (BDNF) expression. Based on findings, it can be concluded that treatment with baicalein and memantine may slow the progression of neurodegeneration in rats.

Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.

The current research work was planned to study the effects of paeonol in the management of diabetic retinopathy. Diabetes was induced in male Sprague Dawley rats using Streptozotocin (55 mg/kg, i.p.). After 4 weeks, the diabetic animals were treated with paeonol at a dose of 50, 100, and 200 mg/kg body weight daily for the next 4 weeks. At the end of treatment, retinal physiology was studied by recording an electroretinogram (ERG); biochemical parameters and oxidative stress were estimated. The histopathology of the retina was also carried out at the end of the study. The ERG of paeonol-treated animals showed a significant improvement in a-wave amplitude, b-wave amplitude, a-wave latency, and b-wave latency (p < 0.001) at 15 cd s/m2 when compared with the diabetic control animals. The paeonol treatment (200 mg/kg) in diabetic animals showed a significant decrease in the plasma glucose level (p < 0.001) when compared to the animals in diabetic control group. Paeonol also significantly decreased the lactate dehydrogenase, aldose reductase, and sorbitol dehydrogenase levels when compared with the diabetic control animals. The oxidative stress in the eye was significantly reduced after the paeonol treatment in the diabetic rats. The histopathology showed a significant reduction (p < 0.05) in the retinal thickness after the paeonol treatment. The results of the study indicate that paeonol can be considered an effective management option for diabetic retinopathy.

Background: Terminalia chebula Retz., Family Combretaceae (T. chebula) is one of the important plants mentioned in Ayurveda, a traditional system of medicine. The present work was designed to study the effect of the aqueous extract of T. chebula fruits in type 2 diabetic rats. Methods: The aqueous extract of the fruits was prepared by the double maceration technique. The extract was subjected to HPTLC analysis, which showed the presence of ellagic acid and gallic acid. Type 2 diabetes was induced in rats with a low dose of Streptozotocin (35 mg/kg) after administering a high-fat diet for fourteen days. Diabetic animals were treated with 500 and 1000 mg/kg of aqueous extract of T. chebula fruits for six weeks. Results: Diabetic rats showed a significantly (511.7 ± 17.6) (p < 0.001) high plasma glucose level compared to the normal group (106 ± 3.358). The T. chebula treatment group showed a significant (p < 0.001) reduction in plasma glucose at 500 mg/kg (394.3 ± 10.35) and 1000 mg/kg (368.6 ± 30.08) doses when compared with the diabetic control group. Treatment with aqueous extract significantly reduced lipid parameters in diabetic animals when compared to the animals in the diabetic control group. Treatment with extract at a dose of 500 mg/kg and 1000 mg/kg showed a significant reduction in AST (p < 0.01, p < 0.001) when compared with diabetic control rats. Treatment with extract significantly reduced ALT at 500 mg/kg (p < 0.05) and 1000 mg/kg (p < 0.001) doses when compared with diabetic control rats. The extract treatment improved insulin sensitivity and insulin sensitivity index (ISI) and significantly decreased HOMR-IR. Treatment with T. chebula aqueous extract at 1000 mg/kg significantly increased the level of GSH (p < 0.05) when compared to diabetic control rats. T. chebula treatment at 1000 mg/kg significantly increased levels of CAT (p < 0.01). Histopathology of pancreatic tissue revealed that the extract has a protective effect against the damage caused by hyperglycemia. Immunohistochemistry of pancreatic tissue showed increased expression of SIRT1 in diabetic animals treated with the extract. Conclusions: The results of the present study indicate that the extract of T. chebula has significant effects in the management of type 2 diabetes.

Alzheimer’s disease (AD) is a neuronal condition causing progressive loss of memory and cognitive dysfunction particularly in elders. An upsurge in the global old age population has led to a proportionate increase in the prevalence of AD. The current treatments for AD are symptomatic and have debilitating side effects. A literature review and current research have directed scientists to explore natural products with better safety and efficacy profiles as new treatment options for AD. Baicalein, belonging to the flavone subclass of flavonoids, has been reported for its anti-oxidant, anti-inflammatory, AChE enzyme inhibitory activity and anti-amyloid protein aggregation activity, which collectively demonstrates its benefits as a neuroprotective agent. Presently, memantine, a NMDAR antagonist, is one of the important drugs used for treatment of Alzheimer’s disease. The current study aims to investigate the effect of baicalein in combination with memantine in β-amyloid-induced AD in albino Wistar rats. Baicalein (10 mg/kg) alone, 5 mg/kg and 10 mg/kg in combination with memantine (20 mg/kg) was administered for 21 days. Treatment with baicalein in combination with memantine showed significant improvement in behavioural studies. The combination treatment decreased oxidative stress, β-amyloid plaque formation and increased the expression of brain-derived neurotrophic factor (BDNF) in the brain. From the results, it can be concluded that treatment with baicalein and memantine could be beneficial for reducing the progression of neurodegeneration in rats. Baicalein has an additive effect in combination with memantine, making it a potential option for the treatment of AD.

Diabetic retinopathy is one of the most prevalent complications of diabetes affecting a large number of people worldwide. Triphala churna – an Ayurvedic formulation consisting of powder of three fruits, Emblica officinalis, Terminalia bellirica and Terminalia chebula has potent antioxidant and anti-diabetic properties. Hence, the study was designed to evaluate the effect of Triphala churna in diabetic retinopathy.Diabetes was induced in rats with streptozotocin (55 mg/kg, i.p.). After four weeks of induction, animals were treated with Triphala churna powder mixed in a vehicle at a dose of 250, 500, and 1000 mg/kg for the next four weeks. At the end of the study, plasma glucose, lactate dehydrogenase levels were determined. Sorbitol dehydrogenase, aldose reductase, and oxidative stress parameters were determined in lens tissues. Electroretinography was carried out. Histopathology study of the retina was studied at the end of the study.Triphala churna significantly reduced plasma glucose and lactate dehydrogenase levels. Triphala significantly reduced sorbitol dehydrogenase, aldose reductase, and oxidative stress in lens tissues. Furthermore, Triphala significantly increased ‘a′ wave and ‘b′ wave amplitude with a reduction in the latencies. The retinal thickness was significantly reduced in Triphala-treated animals. From the results, it can be concluded that Triphala churna delays the progression of retinopathy in diabetic rats.

Recent evidences indicate that there is a substantial increase in worldwide cases of dementia. Alzheimer’s disease is the leading cause of dementia and may contribute to 60–70% of cases. Quercetin is a unique bioflavonoid that has numerous therapeutic benefits such as anti-allergy, anti-ulcer, anti-inflammatory, anti-hypertensive, anti-cancer, immuno-modulatory, anti-infective, antioxidant, acetylcholinesterase inhibitory activity, neuroprotective effects, etc. In the present study, we evaluated the neuroprotective effect of orally administered quercetin with memantine in albino Wistar rats after inducing neurotoxicity through AlCl3 (100 mg/kg, p.o.). Chronic administration of AlCl3 resulted in poor retention of memory and significant oxidative damage. Various behavioral parameters, such as locomotor activity, Morris water maze, elevated plus maze, and passive avoidance test, were assessed on days 21 and 42 of the study. The animals were euthanatized following the completion of the last behavioral assessment. Various oxidative stress parameters were assessed to know the extent of oxidative damage to brain tissue. Quercetin with memantine has shown significant improvement in behavioral studies, inhibition of AChE activity, and reduction in oxidative stress parameters. Histopathological studies assessed for cortex and hippocampus using hematoxylin and eosin (H&E), and Congo red stain demonstrated a reduction in amyloid-β plaque formation after treatment of quercetin with memantine. Immunohistochemistry showed that quercetin with memantine treatment also improved the expression of brain-derived neurotrophic factor (BDNF) and inhibited amyloid-β plaque formation. The present study results demonstrated protective effects of treatment of quercetin with memantine in the neurotoxicity linked to aluminum chloride in albino Wistar rats.

Neuropathy is a common complication of diabetes affecting a large number of people worldwide. Triphala churna is a formulation mentioned in Ayurveda-a traditional system of medicine. It is a simple powder formulation consisting of powders of three fruits, Emblica officinalis L., Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Individual components of Triphala churna have anti-diabetic and antioxidant activities. Hence, this study was designed to evaluate the effect of Triphala churna on diabetic neuropathy. Diabetes was induced with streptozotocin (STZ, 55 mg/kg, i. p.) in rats. Animals were grouped and treated orally with Triphala churna at a dose of 250, 500, and 1,000 mg/kg after 6 weeks of diabetes induction for the next 4 weeks. At the end of study, parameters such as body weight, plasma glucose level, motor nerve conduction velocity were determined. The effect of Triphala churna on thermal hyperalgesia, mechanical hyperalgesia, and mechanical allodynia was also determined at the end of study. The plasma cytokine levels like TGF-β1, TNF-α, and IL-1β were determined by ELISA assay. Histopathology study of the sciatic nerve was studied. Western blotting was performed to study the expression of neuronal growth factor.Treatment with Triphala churna showed a significant reduction in plasma glucose and a significant rise in body weight. Triphala treatment significantly increased the motor nerve conduction velocity and decreased the thermal and mechanical hyperalgesia, as well as mechanical allodynia. The treatment significantly inhibited levels of circulatory cytokines like TGF-β1, TNF-α, and IL-1β. Histopathology study confirmed the neuroprotective effect of Triphala churna. The expression of NGF was significantly increased in sciatic nerves after treatment with Triphala churna. From the results, it can be concluded that Triphala churna delays the progression of neuropathy in diabetic rats.

Currently, phytoconstituents have been emerged as a scientific interest in discovering novel therapeutics against numerous diseases. Berberine is a bioactive alkaloid, historically reported for pharmacological actions such as diuretic, antidiarrheal, antimicrobial and antiprotozoal etc. Scientific evidences exhibit its versatile therapeutic uses against several metabolic, cardiac and neurologic disorders. Despite of valuable properties, the clinical use of berberine has been limited due to its poor intestinal absorption, low bioavailability and limited penetration. Therefore, it demands development of efficient delivery systems to overcome its limitations. This article not only focuses on mode of actions, physicochemical, pharmacokinetic and pharmacodynamic properties of berberine, but also highlights the attempt made so far to deliver it through conventional and novel formulations. Here, a structured division has been briefed, rendering conventional, lipid-based, polymeric-based and miscellaneous berberine formulation. Although extensive in-vitro and preclinical studies have been reported, commercial exploitation of berberine needs in-depth clinical safety and efficacy data.

Acetylcholinesterase (AChE) is an enzyme involved in the progression of Alzheimer's disease (AD). Cardamom oil (CO) has been reported to have acetylcholinesterase inhibitory, antioxidant and anti-anxiety effects. Hence, we studied the effect of cardamom oil in aluminum chloride induced neurotoxicity in rats. AD like symptoms were induced in Wistar rats with aluminum chloride (100 mg/kg, p.o.). Cardamom oil was administered concomitantly by oral route at doses of 100 and 200 mg/kg for 42 days. Behavioral parameters like Morris water maze, elevated plus maze, passive avoidance test and locomotor activity were evaluated on day 21 and 42. AChE activity, oxidative stress parameters, histopathological studies and immunohistochemistry studies were carried out in hippocampus and cortex. Cardamom oil treatment showed significant improvement in behavioral parameters, inhibition of AChE activity (p < 0.001) and reduction in oxidative stress in the brain. Histopathological studies of hippocampus and cortex by hematoxylin & eosin (H. & E.) and congo red stain showed inhibition of neuronal damage and amyloid β plaque formation with cardamom oil treatment. Immunohistochemistry showed, CO treatment inhibited amyloid β expression and upregulated brain-derived neurotrophic factor (BDNF). The present study showed that, cardamom oil has neuroprotective effect in aluminum chloride induced neurotoxicity linked with inhibition of AChE activity and reduction in oxidative damage. This effect of cardamom oil may be useful in management of Alzheimer's disease.

Type 2 diabetic mellitus is a multifactorial metabolic disorder affecting huge population around the world. This indicates that there is an urgent unmet need of cost effective, new treatment strategies for type 2 diabetes mellitus with no or less side effects. Phenolic compounds including isoflavones are known for their beneficial effect in metabolic disorders. The present work was intended to find out efficacy of formononetin, an isoflavone treatment in experimental model of type 2 diabetes. Type 2 diabetes mellitus was induced by feeding high fat diet for 2 weeks prior to streptozotocin administration in Sprague Dawley rats. Diabetic animals were treated with formononetin for 28 days at three dose level, i.e., 10, 20, and 40 mg/kg body weight orally. The effect of formononetin treatment on various parameters such as plasma glucose, glucose tolerance, insulin, HOMA-IR, lipid profile, hepatic glycogen content, glycohaemoglobin and SIRT1 expression in pancreatic tissue was measured. Histopathological changes in pancreatic tissue were also studied. Results of the study demonstrate that formononetin treatment reduces blood glucose level significantly (p < 0.001) at all the three dose level. It also improved glucose tolerance, insulin sensitivity and lipid profile along with reduction in glycohaemoglobin content in blood. Formononetin treatment also improved hepatic glycogen level profoundly in diabetic rats. Determination of SIRT1 expression in pancreatic tissue by immunohistochemical analysis showed that formononetin treatment increases the expression of SIRT1 in pancreatic tissue. Histopathological study showed that treatment with formononetin protects pancreatic beta cells from necro-degeneration and atrophic effect. It can be concluded that formononetin treatment reduces insulin resistance and attenuate hyperglycemia in type 2 diabetes which may be due to increasing expression of SIRT1 in pancreatic tissues.

Diabetes is a metabolic disorder affecting large percentage of population worldwide. NF-κβ plays key role in pathogenesis of vascular complications of diabetes. Persistent hyperglycemia activates NF-κβ that triggers expression of various cytokines, chemokines and cell adhesion molecules. Over-expression of TNF-α, interleukins, TGF-β, Bcl2 and other pro-inflammatory proteins and pro-apoptotic genes by NF-κβ is key risk factor in vascular dysfunction. NF-κβ over-expression also triggers calcification of endothelial cells leading to endothelial dysfunction and further vascular complications. Inhibition of NF-κβ pro-inflammatory pathway is upcoming novel target for management of vascular complications of diabetes. Various natural and synthetic inhibitors of NF-κβ have been studied in management of diabetic complications. Recent preclinical and clinical studies validate NF-κβ as promising target in the management of vascular complications of diabetes.

Objective: To prepare naringenin herbosome and evaluate its antidiabetic activity. Methods: Herbosomes were prepared by the solvent evaporation method. In vitro parameters like particle size, polydispersity index, zeta potential, and entrapment efficiency were estimated and in vitro diffusion study was performed. The in vivo studies were also performed in streptozotocin-induced diabetic male Sprague Dawley rats to evaluate blood glucose, total cholesterol, triglyceride, blood urea nitrogen, total protein, albumin level, aspartate aminotransferase, and alanine aminotransferase levels. Results: The optimized herbosome batch showed a particle size of 564.4 nm, a polydispersity index of 0.412, and zeta potential of -39.3 mV. The percentage entrapment of this formulation was 84.04%, with complete drug release within 8 h. Treatment of diabetic rats with naringenin herbosomes for 28 d significantly reduced the elevated level of plasma glucose as compared to plain naringenin. In biochemical parameters, the treatment showed a significant decrease in total cholesterol, triglyceride, and blood urea nitrogen; while elevated levels of aspartate aminotransferase and alanine aminotransferase were returned to normal. Pure naringenin and herbosome formulation at high dose increased the total protein whereas albumin level significantly increased in naringenin herbosomes at the highest dose but not in the pure naringenin treatment group. Conclusions: Naringenin herbosomes could improve the metabolic profile of diabetic rats, indicating enhanced antidiabetic activity of herbosome formulation.

Objective: To evaluate the effect of formononetin on type 2 diabetic cardiomyopathy. Methods: Diabetes was induced by feeding high-fat diet for 2 weeks and administration of 35 mg/kg of streptozotocin in rats. Formononetin was administered at 10, 20 and 40 mg/kg for 16 weeks once a day. Plasma glucose, lipid parameters, and cardiac markers in blood samples were measured. Body weight and relative heart weight were recorded. Hemodynamic parameters, oxidative stress parameters and silence information regulator 1 (SIRT1) expression in cardiac tissue were estimated. Histopathological changes in cardiac tissue were also observed. Results: Formononetin significantly reduced the levels of glucose, triglycerides, cholesterol, low density lipoprotein, creatine kinase- MB, lactate dehydrogenase and aspartate aminotransferase. In addition, formononetin significantly improved hemodynamic parameters, alleviated oxidative stress and increased SIRT1 expression. Conclusions: The study indicates that formononetin can improve hyperglycemia and hyperlipemia, reduce oxidative stress and increase SIRT1 expression. It can be a potential therapeutic agent for diabetic cardiomyopathy.

Due to increasing need of using distributed databases, high demand presents on sharing data to easily update and access the useful information without any interruption. The sharing of distributed databases causes a serious issue of securing information since the databases consist of sensitive personal information. To preserve the sensitive information and at the same time, releasing the useful information, a significant effort is made by the researchers under privacy preserving data publishing that have been receiving considerable attention in recent years. In this work, a new privacy measure, called c-mixture is introduced to maintain the privacy constraint without affecting utility of the database. In order to apply the proposed privacy measure to privacy preserving data publishing, a new algorithm called, CPGEN is developed using genetic algorithm and multi-objective constraints. The proposed multi-objective optimization considered the multiple privacy constraints along with the utility measurement to measure the importance. Also, the proposed CPGEN is adapted to handle the cold-start problem which commonly happened in distributed databases. The proposed algorithm is experimented with adult dataset and quantitative performance is analyzed using generalized information loss and average equivalence class size metric. From the experimentation, we proved that the proposed algorithm maintained the privacy and utility as compared with the existing algorithm. Keywords: Privacy, Utility, Distributed databases, Data publishing, Optimization, Sensitive information

Introduction: Diabetic Foot ulcer is the commonest burning problem in the society. Many histopathological studies show prolonged inflammatory phase in diabetic wounds. In Sushruta Samhita, Vimlāpanakarma (gentle massage) quoted, as first line of treatment for Vranashotha (inflammation). Case Report: A 70 yrs old male patient, presented with complaints of ulcer associated with severe pain and reddish skin discoloration over ventral aspect of 3 rd toe of right foot since 2 months. Vimlāpanakarma performed with Jātyādi taila around the wound for about 15-20 minutes daily for 10 days and follow-up done for period of 45 days. Discussion: By Vimlāpanakarma with Jātyādi taila there will be raised local temperature, due to which vasoconstriction is relieved and necessary nutrients, oxygen, insulin etc. are carried to the wound site, thereby improving the anoxic condition of wound. Conclusion: Vimlāpanakarma showed significant role in wound healing of Diabetic Foot ulcer, in a short period of time 10 days with no recurrence seen till 45 days follow-up.

Background: Jyotishmati, scientifically known as Celastrus paniculatus Wild (Celastraceae) is one of the most important medicinal plants in Ayurveda. The plant has shown significant pharmacological activities like anti-arthritic, wound healing, hypolipidemic, and antioxidant. Objective: To study possible effects of alcoholic extract of Celastrus paniculatus seeds (AlcE) in experimentally induced pain and inflammation in mice. Materials and Methods: The antinociceptive activity was evaluated in Swiss albino mice by tail immersion, hot plate, and acetic-acid-induced writhing tests at doses of 250, 500, and 1,000 mg/kg. Anti-inflammatory activity was evaluated in model of carrageenan-induced acute plantar inflammation in Wistar rats. Results: In tail immersion test, AlcE showed significant (P < 0.05) increase in tail withdrawal response at dose of 250 mg/kg with maximum possible effect of 15.71%. The maximum possible effect of 23.32% and 30.16% (P < 0.001) was seen at dose of 500 and 1000 mg/kg at 3 hours after administration of extract, respectively. In hot plate test, increase in paw licking time was reported at dose of 500 and 1000 mg/kg. AlcE (1,000 mg/kg) showed maximum response (6.23 ± 0.46) when compared with control (3.20 ± 0.18) at 90 min. In acetic acid induced writhings, AlcE at dose of 250, 500, and 1,000 mg/kg body weight showed 32.35%, 49.01%, and 58.82% inhibition in writhings, respectively. AlcE treated animals (500 and 1,000 mg/kg) showed significant decrease in paw edema at 3 hours and 4 hours, when compared with control animals. Conclusion: Jyotishmati seed extract possesses significant antinociceptive and anti-inflammatory activity.

While there are targeted treatments for triple positive breast cancers, lack of specific biomarkers for triple-negative breast cancers (TNBC) has hindered the development of therapies for this subset of cancers. In this study, we evaluated the anticancer properties of cardiac glycoside Digitoxin (Dtx) and its synthetic analog MonoD on breast cancer cell lines MCF-7 (estrogen receptor-positive breast cancer) and MDA-MB-468 (triple-negative breast cancer). Both cardiac glycosides, at concentrations within the therapeutic range, increased the fraction of cells in the G 0 /G 1 phase of the cell cycle, decreased viability, and inhibited the migration of MCF-7 and MDA-MB-468 cells. Both cardiac glycosides increased production of superoxide and induced apoptosis in both cell types. Reduced protein levels of nuclear factor kappa B and IkappaB kinase-beta were found in cardiac glycoside-treated cells, indicating that the cellular effects of these compounds are mediated via nuclear factor kappa B pathway. This study demonstrates the cytotoxic potential of digitoxin, and more importantly its synthetic analog MonoD, in the treatment of triple-positive breast cancer and more importantly the aggressive triple-negative breast cancer. Collectively, this study provides a basis for the reevaluation of cardiac glycosides in the treatment of breast cancer and more importantly reveals their potential in the treatment of triple-negative breast cancers.

This is the era of fast foods. Irregularity in food timing, improper diet, and mental stress coupled with a sedentary life disturb the digestive system resulting in increased incidence of hemorrhoids. In the present report, we present two cases of intero-external hemorrhoids. Case 1: A 30-year old young male approached with intero-external hemorrhoid at 11 O′clock position as a primary. Case 2: A 41-year-old female visited with second degree intero-external hemorrhoid at 11 O′clock position. Hemorrhoids present in these patients can be considered as Kaphaja Arṣa. These cases were diagnosed by per rectal digital and proctoscopic examinations by ayurvedic proctologists. In both cases, application of Jîmūtaka Lepa was done under local anesthesia administered using lignocaine 2% with adrenaline. This was followed by manual anal dilatation. Jîmūtaka Lepa was applied to the internal hemorrhoids (Arṣa). Changes were observed in the form of edema, ulcer in 3-4 days and sloughing out of the pile mass up to 5-7 days. Subsequently fibrosis of hemorrhoidal masses started after 7 days. Jîmūtaka Lepa shows a significant effect in obliterating the hemorrhoidal mass within a month of application. The patients were followed-up regularly with proctoscopic examination in each visit and did not reveal any evidence of recurrence of the hemorrhoids.

Background: Gmelina arborea Roxb (Verbenaceae), also known as "Gambhari", is an important medicinal plant in the Ayurveda. There are no meticulous scientific reports on effect of the plant on inflammation and pain. Objective: To study the anti-inflammatory and anti-nociceptive properties of aqueous extracts (AE) and methanol extracts (ME) of G. arborea. Materials and Methods: The AE and ME of stembark of G. arborea was prepared by cold maceration and Soxhlet extraction technique respectively. Anti-inflammatory activity was determined in Wistar albino rats in a model of acute plantar inflammation induced by carrageenan. The anti-nociceptive activity was evaluated by using hot plate test and writhing test in Swiss albino mice. Significant differences between the experimental groups were assessed by analysis of variance. Results: AE and ME at dose of 500 mg/kg showed maximum inhibition in carrageenan induced inflammation up to 30.15 and 31.21% respectively. In hot plate test, the AE and ME showed the maximum response of 8.8 ± 0.97 (P < 0.01) and 8.2 ± 1.24 (P < 0.01) respectively at dose of 500 mg/kg when compared with control. AE showed maximum inhibition of writhing response (84.3%) as compared to ME (77.9%) in writhing test at a dose of 500 mg/kg. Conclusion: The findings suggested that G. arborea possess significant anti-inflammatory and anti-nociceptive activities.