Effect of a polyherbal Unani formulation on left ventricular diastolic dysfunction in hypertensive patients - a randomized single blind placebo controlled clinical trial.

OBJECTIVES: Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function. METHODS: This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15 days to assess both subjective and objective parameters in all participants. RESULTS: The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control. CONCLUSIONS: The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

Lycopene potentiates wound healing in streptozotocin-induced diabetic rats.

Background: Diabetes is a growing metabolic disease that is characterized by high blood sugar levels with life-threatening results. Diabetic wounds are a major problem because they do not resolve in few days. Major problems affecting wound healing are infection, age, stress, etc. at the wound site, and other associated disease conditions. Lycopene is a red pigment obtained from various fruits such as tomatoes, watermelon, and guava. It is a powerful antioxidant that scavenges reactive oxygen species and potential as nutraceuticals. It has reported antidiabetic, antioxidant, anti-obesity, anti-inflammatory, antihyperglycemic, and antiaging activities based on the literature. Objective: The objective of the current study is to find the wound-healing potential of lycopene emulgel (LE) and report the properties of the compound. Methods: Wound healing activity was assessed in Streptozotocin induced diabetic rats and control rats. Streptozotocin injection (55 mg/kg) was used to induce marked hyperglycaemia, compared with controls. The formulation was applied topically and was evaluated for efficacy. Results: Treatment of rats with lycopene emulgel (LE) topical application exhibited a significant reduction of wound closure of 95.3 and 88.9% and epithelisation within 21 days. Conclusion: The formulation was found to be novel, safe, and effective in the functional recovery of wounds.

Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. OBJECTIVES: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. METHODS: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1-/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. RESULTS: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1-/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. CONCLUSION: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.

Advances in traditional herbal formulation based nano-vaccine for cancer immunotherapy: Unraveling the enigma of complex tumor environment and multidrug resistance.

Cancer is attributed to uncontrolled cell growth and is among the leading causes of death with no known effective treatment while complex tumor microenvironment (TME) and multidrug resistance (MDR) are major challenges for developing an effective therapeutic strategy. Advancement in cancer immunotherapy has been limited by the over-activation of the host immune response that ultimately affects healthy tissues or organs and leads to a feeble response of the patient's immune system against tumor cells. Besides, traditional herbal medicines (THM) have been well-known for their essential role in the treatment of cancer and are considered relatively safe due to their compatibility with the human body. Yet, poor solubility, low bio-availability, and lack of understanding about their pathophysiological mechanism halt their clinical application. Moreover, considering the complex TME and drug resistance, the most precarious and least discussed concerns for developing THM-based nano-vaccination, are identification of specific biomarkers for drug inhibitory protein and targeted delivery of bioactive ingredients of THM on the specific sites in tumor cells. The concept of THM-based nano-vaccination indicates immunomodulation of TME by THM-based bioactive adjuvants, exerting immunomodulatory effects, via targeted inhibition of key proteins involved in the metastasis of cancer. However, this concept is at its nascent stage and very few preclinical studies provided the evidence to support clinical translation. Therefore, we attempted to capsulize previously reported studies highlighting the role of THM-based nano-medicine in reducing the risk of MDR and combating complex tumor environments to provide a reference for future study design by discussing the challenges and opportunities for developing an effective and safe therapeutic strategy against cancer.

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues.

OBJECTIVE: To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. METHODS: The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. RESULTS: HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. CONCLUSION: C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.

Organ wide toxicological assessment of common edible herbs and their mixtures as used in home remedies.

The use of home remedies for medicinal purposes, most of which are edible plants has continued to be a practice in many homes. However, there has been an increasing report of chronic use with lethal effect. Among the commonly used herbal/ medicinal plants were ginger, garlic and lemon. These were seen to be prevalent across continents with brewing and crude extraction being the most means of consumption. This study investigated the organ wide toxicity of this extract following chronic consumption of crude extract. Twenty-five albino Wister rats, five in each group were used for this experiment. Each animal received 0.5ml/kg body weight of either ginger extract, garlic extract, lemon juice, or a mixture of equal volumes of all three extract (v/v) respectively twice daily for seven (7) days. Statistics were represented as ±SE; P≤0.05 was considered significant. Previous studies have shown that moderate consumption of these medicinal plants were beneficial and have shown no deleterious effect. This study observed no change in the weight of the experimental animals. The weight of the animals continued to increase except for the group that received lemon and the mixture, but these were not significant. It was observed that chronic consumption induced organ wide toxicity to include the liver, kidney, intestinal epithelium, stomach, and pancreas. These were shown to alter tissue architecture and the cell morphology. Packed cell volume was reduced in the lemon and the group that received a combination of all extracts (p=o.03). Blood differentials showed changes in levels. An elevated basophil level was observed in ginger and garlic (p<0.0001; p=0.0006). Monocyte levels increased progressively across each group when compared to the control with the most elevated level seen in the group that received the mixture (p<0.0001). Lymphocyte count was reduced across all the groups that received the extract except for animals that received ginger. This study suggests the application of caution among users of these medicinal plants and continues to draw attention to the need for harmonization and standardization of safe use doses.

An In Vitro Evaluation of the Antibacterial Efficacy of Solanum xanthocarpum Extracts on Bacteria From Dental Plaque Biofilm.

OBJECTIVE: The focus of research has recently shifted toward developing herbal-based medicines due to the emerging bacterial resistance and side effects of antibiotics. Solanum xanthocarpum (Sx) is a medicinal plant with potent pharmacological properties. This study aimed to evaluate the antibacterial activity of its crude extracts on bacteria isolated from dental plaque in patients with gingivitis. MATERIALS AND METHODS: Aqueous, ethyl acetate, hexane, chloroform, and ethanolic extracts were prepared from Sx. Dental plaque samples were collected from patients with plaque-induced gingivitis. Disk diffusion assay was performed to determine the antibacterial activity of the extracts at concentrations of 25 mg/ml, 50 mg/ml, and 75 mg/ml with ampicillin 200 mg/ml as a positive control. The minimum inhibitory concentration (MIC) of the aqueous extract was also evaluated by broth dilution test against bacteria isolated from dental plaque biofilm. RESULTS: The antibacterial activity was estimated by measuring the zones of inhibition through the disc diffusion method. The Kruskal Wallis with Dunn post hoc test performed for intergroup comparison between the various extracts showed a statistically significant difference in inhibition of bacterial growth between 25 mg/ml and 75 mg/ml concentrations. There was no significant difference between the 75 mg/ml Sx concentration and the positive control. In addition, the MIC was elucidated to be 0.625 g/ml, at which there was maximum inhibition of bacterial growth. CONCLUSION: The Sx extract exhibited antibacterial activity against periodontal pathogens. Thus, it can be concluded that optimum concentrations of Sx could be used in therapeutic strategies to prevent and manage periodontal diseases.

In Vitro Evaluation of Antioxidant and Anti-inflammatory Potentials of Herbal Formulation Containing Marigold Flower (Calendula officinalis L.) Tea.

Aim To assess the anti-inflammatory and antioxidant properties of Calendula officinalis tea formulation. Materials and methods In this study, a formulation of 2 grams of dried marigold flower petals and 100 milliliters (ml) of distilled water was subjected to anti-inflammatory testing using albumin denaturation assay and anti-protease activity and antioxidant testing by DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay. An independent sample t-test was done to compare the anti-inflammatory and antioxidant potentials of marigold tea formulation and control using SPSS version 22.0 software (IBM Corp., Armonk, NY), and any p-value less than 0.05 was considered statistically significant. Results The highest anti-inflammatory and antioxidant activities of marigold extract were exhibited at 10 microliters (µl) and 20 µl (p-value = 0.002 and 0.000), respectively. The anti-inflammatory activity was higher than the control at all concentrations, whereas the antioxidant activity was higher at lower concentrations when compared to higher concentrations. Conclusion Marigold flower tea formulation exhibited better anti-inflammatory and antioxidant activities than the controls and therefore could be evaluated as a potential therapeutic agent.

Evaluation of Herbal Hair Lotion loaded with Rosemary for Possible Hair Growth in C57BL/6 Mice.

Background: Rosmarinus officinalis (rosemary) is a common household plant with needle-like leaves and white flowers that belongs to the family Lamiaceae and has various medicinal properties including ailments of hair and scalp, cardiovascular, nervous disorders, etc., In the current work, we have focused on formulation and evaluation of 1% hair lotion incorporated with methanolic extract of R. officinalis. Materials and Methods: The aerial parts of the plant were extracted with methanol and then the nature of phytochemicals were identified by chemical tests. It showed the presence of proteins, amino acids, fats and oils, steroids, glycosides, phenolic compounds, flavonoids, volatile oil, and vitamins. The extract was formulated to a suitable hair lotion and then evaluated for its various quality control parameters. Finally, the lotion was evaluated for hair growth promoting activity on C57BL/6 mice, using water as control and 2% minoxidil hair lotion as standard. Results: It was observed that the formulated 1% herbal hair lotion passed all the evaluation parameters and showed a significant hair growth promoting activity than the standard drug-treated animals. Conclusion: Although several researches have been carried out on the rosemary, an investigation on formulation of hair lotion adding the extract of the aerial part of the plant is for the first time. Since our formulation exhibited an excellent activity, it can be well thought out to be an alternative to the commercially available hair growth promoters with a lot of unwanted effects.

Herbal Components Inspiring Current Lifestyle Disease Treatment: Role of Nutraceuticals.

Nutraceuticals are the foods that are used to prevent and cure diseases. Food and nutrients are essential for the body's normal function and aid in the maintenance of an individual's health and prevent various diseases. Nutraceuticals are medicinal foods that aid in the maintenance of health, the enhancement of immunity, and the prevention and treatment of specific diseases. The markets of nutraceuticals are one of the fastest-growing industry segments. The prime reason for this accelerated market growth lies in the fact that nutraceuticals are low cost, can prevent diseases to occur, hence, can save the health care cost, have more nutritional value, and many others. Nutraceuticals can be classified on different foundations based on what they promise, natural sources, and nutraceutical food available in the market. This article will discuss those classifications in detail along with the role of nutraceuticals in lifestyle diseases, regulations, market trends, and prospects of nutraceuticals. The article will also highlight the concern areas which play as the limiting factor in the nutraceuticals industry growth like lack of quality control, lack of data on its working, and many other things.

Traditional Chinese Medicine as the preventive and therapeutic remedy for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic still has tremendous impacts on the global socio-economy and quality of living. The traditional Chinese Medicines (TCM) approach showed encouraging results during previous outbreaks of Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). With limited treatment availability, TCM herbs and formulations could be viable to reduce COVID-19 symptoms and potential sources for discovering novel therapeutic targets. We reviewed 12 TCM herbs and formulations recommended for COVID-19 management by the National Health Commission and National Administration of Traditional Chinese Medicine, the People's Republic of China. This article explored the Chinese national authorities' guidelines from 2003 to 2020, the scientific data in public databases for the recommended TCM remedies, and their potential mechanistic actions in COVID-19 management. Several TCM herbs and formulations could potentially benefit COVID-19 management. The recommended TCM oral preparations list are Huoxiang zhengqi, Jinhua Qinggan, Lianhua Qingwen, and Shufeng jiedu; the recommended injection preparations comprise Xiyanping Xuebijing, Re-Du-Ning, Tanreqing, Xingnaojing, Shenfu, Shengmai, and Shenmai. TCM remedies are viable options for symptom alleviation and management of COVID-19. The current SARS-CoV-2 pandemic presents an opportunity to find novel therapeutic targets from TCM-active ingredients. Despite the recommendations in Chinese National guidelines, these remedies warrant further assessments in well-designed clinical trials for their efficacies in COVID-19.

Aloe-emodin Quantification using HPTLC and RP-UHPLC in Extracts and Commercial Herbal Formulations: Evaluation of Antimicrobial and Antioxidant Effects.

BACKGROUND: High-performance thin-layer chromatography (HPTLC) was developed and validated for the determination of aloe-emodin in accordance with ICH guidelines. In addition, a novel RP-UHPLC method was developed, and both methods were used to analyse the herbal extract and herbal formulation. METHODS: Separation was carried out on a silica gel 60 F254 HPTLC plate using the mobile phase Toluene: Methanol (9:1). The linearity was good across the 800-4000 ng/spot range. Validation results are within acceptable limits. The percent RSD for accuracy was 0.58-1.77, and precision was 1.10-1.97 and 1.45-1.94 for intraday and interday, respectively. The percentage of aloe-emodin found in the herbal extract and aloe vera capsule was 99.83 ± 1.19 and 99.53 ± 1.29, respectively, using this method. RESULTS: Quantification of aloe-emodin in herbal extract and herbal formulation were done using a novel UHPLC method with chromatographic conditions of orthophosphoric acid Methanol (0.1 percent OPA): Water (65:35, v/v) and pH 3, a flow rate of 1.2 ml/min, and elute detection at 254 nm. At 6.32 minutes, a sharp and symmetric peak was observed. The method developed was validated in accordance with ICH guidelines. The percent RSD numerical value of accuracy was 0.304-0.576, and the inter-day and intraday precision were 0.32-3.08 and 0.51-2.78, respectively. Herbal extract and aloe vera capsule were analysed using the new UHPLC method. Aloe-emodin percentages were reported as 100.3 ± 0.89 and 99.53 ± 1.29, respectively. CONCLUSION: The antimicrobial and anti-oxidant activities of an aloe-vera herbal formulation were studied, and the results were positive.

An herbal formulation "Shenshuaifu Granule" alleviates cisplatin-induced nephrotoxicity by suppressing inflammation and apoptosis through inhibition of the TLR4/MyD88/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenshuaifu Granule (SSF) is an in-hospital preparation approved by the Guangdong Food and Drug Administration of China. It has been clinically used against kidney diseases for more than 20 years with a definite curative effect. AIM OF THE STUDY: Cisplatin (CDDP) is a first-line chemotherapeutic drug in clinical practice, primarily excreted by the kidney with nephrotoxicity as a common side effect. Approximately 5-20% of cancer patients develop acute kidney injury (AKI) after chemotherapy; however, prevention and control strategies are currently unavailable. Therefore, it is important to identify safe and effective drugs that can prevent the nephrotoxicity of CDDP. SSF is an herbal formulation with 8 herbs, and has been used to protect the kidney in China. Nonetheless, its mechanism in relieving CDDP nephrotoxicity remains unclear. Therefore, this work attempt to prove that SSF can alleviate CDDP nephrotoxicity. We also explore its mechanism. MATERIALS AND METHODS: First, Thin Layer Chromatography (TLC) of a few herbs in SSF were performed for quality control. Several open-access databases were used to identify the active ingredients of SSF, their corresponding targets, and CDDP-induced nephrotoxicity targets. We performed Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Next, the results of network pharmacology were validated using CDDP-induced nephrotoxicity mouse models. Renal function in the mice was assessed by analyzing the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). On the other hand, renal damage was assessed by determining the level of tubular injury and apoptotic cells using Periodic acid-Schiff (PAS) staining and Terminal Dutp Nick End-Labeling (TUNEL) staining, respectively. The expression of inflammatory and apoptotic-related targets including IL-1ß, IL-6, TNF-α, Cox-2, Bax, Bcl-2, Cleaved-caspase 3, and Cleaved-caspase 9 was determined using Western Blot (WB) and Immunohistochemistry (IHC). Furthermore, WB was used to analyze the expression of proteins associated with the TLR4/MyD88/NF-κB pathway in the kidneys of mice with CDDP-induced nephrotoxicity. Finally, molecular docking simulations were performed to evaluate the binding abilities between major active ingredients of SSF and core targets. RESULT: Through network pharmacology, we identified 127 active ingredients of SSF and their corresponding 134 targets. Additional screening identified 14 active ingredients and 17 targets for further analysis. In biological process (BP), the targets were enriched in inflammation and apoptosis, among others. In KEGG terms, they were enriched in apoptosis and NF-κB pathways. Animal experiments revealed that SSF significantly reduced the levels of Scr and BUN and prevented renal tubular damage in mice treated with CDDP. In addition, SSF inhibited inflammation and apoptosis by targeting the TLR4/MyD88/NF-κB pathway. Molecular docking revealed good binding capacities of active ingredients and core targets. CONCLUSION: In summary, the experimental findings were consistent with the network pharmacological predictions. SSF can inhibit inflammation and apoptosis by targeting the TLR4/MyD88/NF-κB pathway. Taken together, our data suggest that SSF is an alternative agent for the treatment of CDDP-induced nephrotoxicity.

Successful treatment of refractory erythrodermic psoriasis with traditional Thai herbal medicine.

BACKGROUND: Thai herbal formulations have been used traditionally in Thailand for the treatment of psoriasis. However, there is still a lack of scientific data supporting the effects of Thai herbal formulations in psoriasis treatment. OBJECTIVES: This study aimed to demonstrate the therapeutic effects of Thai herbal formulations for the treatment of erythrodermic psoriasis. MATERIALS AND METHODS: All Thai herbal formulations (haematic tonic, lymphatic treatment, skin treatment) were obtained from a traditional Thai medicine doctor, Mr. Somporn Chanwanitsakul. The effects of Thai herbal formulations in a patient with erythrodermic psoriasis were assessed for four weeks. Primary outcome, psoriasis area and severity index (PASI) and secondary outcome, safety data and dermatology life quality index (DLQI) measurements were evaluated at baseline and four weeks. Then, in vitro biological activities (antioxidant, anti-microbial, cytotoxic effects, and anti-inflammatory) of Thai herbal formulations were determined to promote the therapeutic effects. RESULTS: Thai herbal formulations were safe and effective in the treatment of erythrodermic psoriasis and had a modest positive impact on the DQLI of the patient. In addition, in vitro studies have shown that all Thai herbal formulations revealed remarkable anti-oxidant and anti-inflammatory potential to support their therapeutic activities. However, the Thai herbal formulations possessed weak intrinsic antibacterial activities against all tested bacterial strains (MIC and MBC E. coli, S. aureus, S. pyogenes, P. aeruginosa: > 256 µg/ml). CONCLUSION: The findings indicated that successful treatment of erythrodermic psoriasis with Thai herbal formulations was involved in their anti-oxidant and anti-inflammatory activities. They could be considered as an alternative treatment for refractory erythrodermic psoriasis.

Anti-inflammatory potential of turmeric, amla, and black pepper mixture against sepsis-induced acute lung injury in rats.

Acute lung injury (ALI), is a severe inflammatory lung disease. We tested the prophylactic effect of a functional food mix comprising three anti-inflammatory plant products: turmeric, amla, and black pepper (TAB) against lipopolysaccharide (LPS)-induced ALI in rats. Two-month-old male Wistar rats were randomly divided into three groups: control (C), LPS (5 mg/kg), and LPS with TAB (TAB). After 6 h of LPS injection, the rats were sacrificed by cervical decapitation to collect the lung tissue. Results showed that TAB partially ameliorated LPS-induced increase in circulating inflammatory cytokines (TNFα and IL6) and significantly prevented lung histopathological changes. TAB also suppressed LPS-activated ER stress markers (GRP78, pIRE1, and CHOP) and apoptotic markers (caspase-3 and - 12) in the lung. The anti-inflammatory effects of the TAB support its potential use as an adjuvant to mitigate ALI. Importantly, TAB's ingredients have been used for centuries as part of the diet with limited or no toxic effects.

Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation.

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.

Subchronic toxicity study of herbal tea of Moringa stenopetala (Baker f.) Cudof. and Mentha spicata L. leaves formulation in Wistar albino rats.

Background: Moringa stenopetala (Baker f.) Cudof. and Mentha spicata L. are widely used in the traditional system of medicine for the treatment of diabetes, hypertension, digestive problems and various disorders. The leaves formulation of M. stenopetala and M. spicata herbal tea showed better antidiabetic and antihypertensive effects in rodent models. However, its long-term safety profile has not been investigated yet. Thus, this study investigated the subchronic (90 days) oral toxicity of the leaves formulation of M. stenopetala and M. spicata herbal tea in Wistar albino rats. Methods: Four groups of rats (n = 10, with 5/sex/group) were randomly assigned into a control (vehicle) group and three test groups (559.36, 1118.72 and 2237.44 mg/kg, respectively). The three test groups received the herbal tea of M. stenopetala and M. spicata leaves blend daily for 90 days. The control group received distilled water. During the treatment period, clinical signs were observed daily, and food consumption and body weight changes of the rats were measured weekly. At the end of the experiment, macro-pathological, hematological and biochemical parameters were evaluated. Furthermore, histopathology of liver, kidney, heart, stomach and pancreas were examined. Results: Subchronic oral administration of the herbal tea of M. stenopetala and M. spicata leaves blend did not result in death or significant toxicity signs in the treated group rats. Moreover, the herbal tea caused no significant changes on body weight, food intake, organ weight, hematological and biochemical parameters in either sex. However, the serum AST, CK and LDH levels were significantly elevated in rats treated with 2237.44 mg/kg of herbal tea in both sexes. There was no significant alteration in the histology of organs, only minor lesions in the liver, kidney and pancreas were observed. Conclusion: The study results indicate that the herbal tea of M. stenopetala and M. spicata leaves blend is relatively safe/low toxic to rats in subchronic exposure. However, further preclinical (chronic, teratogenic, reproductive and developmental toxicity) studies in animals are required in order to have sufficient safety and toxicity profiles for its use in humans.

Selection of green carrier solvent for the effective creation of bio-inspired liquid formulation and anti-fungal potency evaluation.

Existing pesticide formulation solvents generate volatile organic compounds (VOCs), are combustible, and are classed as hazardous air pollutants (HAPs), meaning they are detrimental to users and phytotoxic to crops. Green solvents are required in formulations due to regulations, health, and environmental concerns. In emulsifiable concentration (EC) formulations, the "green chemistry" movement has led to the use of less harmful solvents. After a detailed and comparative fungal growth inhibition assessment, the least harmful carrier solvent among four regularly used organic solvents [dimethyl sulfoxide (DMSO), dimethylformamide (DMF), aromatic hydrocarbon (C9), and methyl oleate] was chosen in this study. We employed methyl oleate (cis-9-Octadecenoic acid methyl ester) as a bio-based green reserver (60%) to create effective bioinspired EC formulations (30%) of Pongamia pinnata L extract utilising emulsifier blends (10 percent) based on the known toxicity order (DMF > DMSO > C9 > methyl oleate). EC1 outperformed the other thirteen formulations (EC1-EC13) in terms of emulsion stability, cold test, accelerated storage stability, flash point, and other metrics, proving its suitability for commercial production. Using four therapeutically appropriate concentrations of agricultural usage, in-vitro fungicidal effects against Alternaria solani and Phytophthora spp. were examined.A. solani (EC50 = 0.08 percent) showed the greatest growth suppression (87.4 percent) at the maximum dosage (1 percent), followed by Phytophthora sp. (71.1 percent) (EC50 = 0.49 percent). The study proved its utility in the production of environmentally acceptable green solvent-based herbal formulations as a long-term crop protection alternative to harmful chemical pesticides.

Acute and subacute toxicity studies of a poly herbal formulation used for diabetes.

Objectives: PHF-dia (Poly Herbal Formulation Diabetes) is a polyhedral formulation possessing antihyperglycemic and antihyperlipdimic effects. This study aims to assess acute and sub-acute toxicity of PHF-dia in rats. Methods: This is an experimental study conducted in two different phases. Acute toxicity was conducted for 14 days and sub-acute toxicity was conducted for 28 days. Both studies were conducted in animal house of Jinnah University for Women, Karachi, Pakistan. Acute toxicity was evaluated in vivo with single time oral administration of 400 mg/kg and 2000 mg/kg doses for two weeks. Sub-acute toxicity was investigated with the application of repeated doses of 150 mg/kg/day, 250 mg/kg/day and 500 mg/kg/day for 28 days. Results: Acute toxicity study results showed no toxic symptoms, behavioral changes or death in rats up to 2000 mg/kg. Therefore, LD50 of oral toxic dose must be more than 2000 mg/ml. Similarly, sub-acute toxicity studies confirmed the safety of PHF-dia and showed no clinical symptoms nor biochemical or histological variation in rats treated with 150 mg/kg, 250 mg/kg and 500 mg/kg compared to the control group (p <0.05). Conclusion: This indicates safe nature of PHF-dia for the further clinical trials. However, mechanism of action of PHF-dia is not fully understood.

Polyherbal formulation exerts wound healing, anti-inflammatory, angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers.

Diabetic foot ulcer (DFU) is a common and devastating complication in diabetic patients and is associated with an elevated risk of amputation and mortality. DFU remains a major therapeutic challenge due to poor understanding of its underlying pathogenesis. This complication is characterized by impaired wound healing; however, mechanisms causing this impairment are complicated and involve interactions between many different cell types and infections. In addition to other conventional DFU treatments, herbal foot baths are also common, although little is known about their mechanisms of action, and they contain a wide variety of herbal ingredients. In this study, we aimed to examine the effects of three polyherbal formulations consisting of medicinal plants used in traditional Thai herbal foot baths on wound healing, anti-inflammation, angiogenesis, and extracellular matrix modulation using high-concentration glucose-treated human keratinocytes, in addition to antibacterial evaluation. Our results showed that formulation 3 (F3) possessed the greatest potential to restore the impairment of keratinocytes caused by high glucose concentrations. We found that F3 could inhibit the growth of Staphylococcus aureus, accelerate wound healing, and upregulate the expression of TIMP-1, VEGF, and TGF-ß, and downregulate the expression of TNF-α, IL-6, and MMP-9. Collectively, these data support the potential of F3 for therapeutic development in the treatment of DFU.