Anti-inflammatory and modulatory effects of steroidal saponins and sapogenins on cytokines: A review of pre-clinical research.

BACKGROUND: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models. PURPOSE: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines. STUDY DESIGN AND METHODS: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved. RESULTS: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways. CONCLUSION: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Volatile profiling and UHPLC-QqQ-MS/MS polyphenol analysis of Passiflora leschenaultii DC. fruits and its anti-radical and anti-diabetic properties.

Twenty-four phenolic compounds including daidzein, epicatechin and artepillin C were identified in Passiflora leschenaultii DC. fruit by UHPLC-QqQ-MS/MS analysis. The aroma profile has been studied using the HS-SPME/GC-MS which revealed 67 volatile compounds including 13 terpenes, 18 alcoholics, 15 esters, ketones and phenolic acids. Further, the proximate composition, anti-radical and anti-diabetic activities of fruit pulp were also determined. The fresh fruit pulp of P. leschenaultii registered higher total phenolic (691.90 mg GAE/g extract) and tannin (313.81 mg GAE/g extract) contents and it also exhibited maximum DPPH (IC50 of 6.69 µg/ml) and ABTS+ (9760.44 µM trolox equivalent/g extract) scavenging activities. The fresh fruit pulp showed a strong inhibition towards the α-Amylase and α-Glucosidase (IC50 of 32.20 and 19.81 µg/mL, respectively) enzymes. Thus, the work stipulates that phenolic compounds rich P. leschenaultii fruit can serve as a potential nutraceutical, antioxidative and anti-diabetic agent in food and pharmaceutical formulations.

Levan production from sucrose using chicken feather peptone as a low cost supplemental nutrient source.

Chicken feather peptone (CFP) derived from poultry waste is a rich source of essential minerals and amino acids. This, along with suitable carbon source, can be used as a low cost complex supplemental nutrient source for microbial fermentation. In the present work, CFP blended with sucrose was evaluated for the production of levan using Bacillus subtilis MTCC 441. Amount of CFP added to the medium significantly influenced levan production and it was found that at a concentration 2 g/L, maximum levan yield of 0.26 ±â€¯0.04 g/g sucrose was obtained. The levan yield obtained with CFP as a low cost supplemental nutrient source was comparable with that obtained from commercial medium (0.31 ±â€¯0.02 g/g sucrose). Levan produced using CFP was tested on primary cell lines at various concentrations (100-1000 µM) and found to be non-toxic and bio-compatible in nature. This indicates that CFP could be used as low cost nutrient source for levan production.

Eplingiella fruticosa (Lamiaceae) essential oil complexed with ß-cyclodextrin improves its anti-hyperalgesic effect in a chronic widespread non-inflammatory muscle pain animal model.

Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with ßCD (HypEO-ßCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, ß-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-ßCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-ßCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with ß-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.

Protective effects of flavonoid composition rich P. subpeltata Ortega. on indomethacin induced experimental ulcerative colitis in rat models of inflammatory bowel diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyphenolics (flavonoid and phenolic) rich plants are the effective source for the treatment of acute and chronic degenerative diseases including inflammatory bowel disease. OBJECTIVE: This study was aimed to examine the effects of polyphenolics rich leaf acetone extract of P. subpeltata against the indomethacin induced ulcerative colitis in rats. MATERIALS AND METHODS: Two consecutive days administration of indomethacin produced chronic inflammation in GIT tissues of rats. Further, the plant extract 200 and 400 mg/kg treatment were continued until 11th day. Then hematological, enzymatic antioxidants, MPO and histological evaluations were analyzed. Moreover, the extracts were treated with RAW267.4 cells for the cytotoxicity, NO and TNF-α analysis. RESULTS: The obtained results revealed, that higher dose of the plant extract dropped neutrophil infiltration followed by inhibiting the MPO enzyme levels and controls the enzymatic antioxidants such as SOD, CAT, GSH and LPO. RAW cells study also proved that the plant extract effectively inhibits NO and TNF-α production. CONCLUSIONS: Thus, these results suggest that P. subpeltata extract may have therapeutic potential for the treatment of IBD although further clinical research is still warranted.

Effect of spray drying on bioactive and volatile compounds in soursop (Annona muricata) fruit pulp.

Soursop is seasonal and highly perishable fruit, which limits its commercialization. Thus it is necessary to conserve its pulp so that it is available throughout the year. One of the most common forms of fruit preservation is by dehydration. This work had an objective to dehydrate soursop pulp by spray drying at optimum conditions and to analyze the retention of bioactive and volatile compounds in soursop powder, besides analyzing its antioxidant capacity. The total phenolics, carotenoids and flavonoids contents were determined, while volatile compounds were analyzed by Stir Bar Sorptive Extraction (SBSE) coupled with GC-MS system. The total content of the phenolic compounds and flavonoids in the fresh pulp were 160.28 mg of GAE/100 g and 87.17 mg of quercetin/100 g, respectively while for rehydrated dried powder their values were 158.95 mg of GAE/100 g and 85.17 mg of quercetin/100 g, respectively. The total phenolic compounds, flavonoids and antioxidant capacity did not show any significant difference (p < .05) between the fresh fruit pulp and dehydrated powder. A total of 85 volatile compounds were identified, of which 33 were esters, representing the major class of organic compounds, 15 were terpenes, 10 aldehydes, 7 acids, 5 alcohols, 5 lactones, 3 ketones, and 6 other compounds. Of the total 85 compounds, identified in soursop pulp, 58 compounds were identified in the rehydrated dried powder. The principal compounds for both samples were methyl (E)-2-hexenoate, methyl hexanoate and methyl (E)-2-butanoate, which contribute to soursop aroma according to their Odor Active Values (OAV). Considering that there was no significant difference (p < .05) between fresh pulp and the rehydrated dried powder in concentrations of bioactive compounds and even with the reduction in the concentration of the main volatile compounds while the OAVs of these compounds were relatively high, it is concluded that spray dried powder of soursop pulp retains its nutritional and aroma quality, besides maintaining the antioxidant capacity.

Evaluation of Aristolochia indica L. and Piper nigrum L. methanol extract against centipede Scolopendra moristans L. using Wistar albino rats and screening of bioactive compounds by high pressure liquid chromatography: a polyherbal formulation.

The present study was aimed to explore the anti-venom activity of Aristolochia indica and Piper nigrum plants against the centipede (Scolopendra moristans) envenomation in animal model. In vtiro phytochemical, antioxidant and blocking of proteolysis were carried out by using standard spectrophotometric methods. In vivo anti-venom activity of methanol extracts was determined using Wistar albino rats after fixing lethal and effective doses. The electrolytes, lipid, liver, kidney, hematological parameters were analyzed and histopathology of skin and liver were also examined. Anti-skin cancer by MTT method and HPLC analysis were also carried out. The CAIPN extract showed higher total phenolics (150.65 ± 0.08 mg GAE/g extract) and flavonoids (158.97 ± 0.93 mg RE/g extract) content. Further, the same extract revealed the higher molybdenum reducing, inhibition of lipid peroxidation (80.08 ± 0.22%), DPPH radical scavenging (3.05 µg/mL), and blocking of proteolysis activities (96.45 ± 0.04%). The parameters like hypersensitivity, electrolytes, lipids, blood components, liver and kidney marker of the CAIPN methanol extract (200 mg/kg) treated envenomated rats was remarkable and same as in the normal animals. Such status was also achieved by RBAI and SPN at 600 mg/kg. The histopathological scoring of skin and liver confirmed the venom neutralizing activity of CAIPN. Also, the CAIPN methanol extract was notable in anti-skin cancer activity (208 µg/mL). The presence of the ferulic acid (04 ± 0.09 µg/mg) and quercetin (35.30 ± 0.30 µg/mg) like compounds was confirmed by HPLC analysis. Hence, the present investigation results conclude that the CAIPN was significant in their action and this polyherbal formulation could be considered as a new source for the pharmaceutical industries to develop a new effective, ecofriendly anti-venom drug.

Nutrient removal and energy production from aqueous phase of bio-oil generated via hydrothermal liquefaction of algae.

Removal of nutrients (phosphorus and nitrogen) as struvite from bio-oil aqueous phase generated via hydrothermal liquefaction of algae was evaluated in this study. Effect of process parameters such as pH, temperature and reaction time on struvite formation was studied. More than 99% of phosphorus and 40-100% ammonium nitrogen were removed under all experimental conditions. X-ray diffraction analysis confirmed the formation of struvite, and the struvite recovered from bio-oil aqueous phase can be used as a slow-release fertilizer. Biogas production from struvite recovered bio-oil aqueous phase showed 3.5 times higher CH4 yield (182±39mL/g COD) as compared to non-struvite recovered aqueous phase. The results from this study indicate that both struvite and methane can be produced from bio-oil aqueous phase.

Polyphenols rich Passiflora leschenaultii leaves modulating Farnesoid X Receptor and Pregnane X Receptor against paracetamol-induced hepatotoxicity in rats.

The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed. The assessment revealed that the acetone extract significantly reduced the elevated levels of SGPT, SGOT and ALP in serum. Moreover, the enzymatic antioxidants such as SOD, CAT and LPO were also retained normally by the plant extract. From histopathological analysis, it was clearly evident that the cellular architecture of plant extract treated rat liver tissues were not affected by the paracetamol induction at the higher dose. The results of docking studies also revealed that the identified compounds showed steric interactions (between nonpolar atoms) with amino acid groups. Collectively, the present study suggests that P. leschenaultii leaves extract protects the liver from paracetamol induced hepatic damage.

Natural products assessed in animal models for orofacial pain – a systematic review

ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

Enhancement of orofacial antinociceptive effect of carvacrol, a monoterpene present in oregano and thyme oils, by ß-cyclodextrin inclusion complex in mice.

Orofacial pain is associated with diagnosis of chronic pain of head, face, mouth, neck and all the intraoral structures. Carvacrol, a naturally occurring isoprenoid with diverse class of biological activities including anti-inflammatory, analgesic, antitumor and antioxidant properties. Now, the antinociceptive effect was studied in mice pretreatment with carvacrol (CARV) and ß-cyclodextrin complex containing carvacrol (CARV-ßCD) in formalin-, capsaicin-, and glutamate- induced orofacial nociception. Mice were pretreated with vehicle (0.9% Nacl, p.o.), CARV (10 and 20mg/kg, p.o.), CARV-ßCD (10 and 20mg/kg, p.o.) or MOR (10mg/kg, i.p.) before the nociceptive behavior induced by subcutaneous injections (s.c.) of formalin (20µl, 2%), capsaicin (20µl, 2.5µg) or glutamate (20µl, 25µM) into the upper lip respectively. The interference on motor coordination was determined using rotarod and grip strength meter apparatus. CARV-ßCD reduced the nociceptive during the two phases of the formalin test, whereas CARV did not produced the reduction in face-rubbing behavior in the initial phase. CARV-ßCD (20mg/kg, p.o.) produced 49.3% behavior pain while CARV alone at 20mg/kg, p.o, produced 28.7% of analgesic inhibition in the second phase of formalin test. CARV, CARV-ßCD and Morphine (MOR) showed a significant reduction against nociception caused by capsaicin or glutamate injection. Thus the encapsulation of carvacrol in ß-cyclodextrin can acts as a considerable therapeutic agent with pharmacological interest for the orofacial pain management.

Effects of luteolin and quercetin 3-ß-d-glucoside identified from Passiflora subpeltata leaves against acetaminophen induced hepatotoxicity in rats.

Passiflora subpeltata has many beneficial effects in the treatment of various diseases including inflammation, pain and fever. This study was aimed to analyze the phytochemical compounds present in acetone extract of P. subpeltata leaves and to evaluate their performance against paracetamol induced hepatotoxicity activity. HPLC-DAD method was used to identify and quantify the phytochemical compounds. Hepatoprotective activity of acetone extract in the treatment of rat liver functions was monitored by the measurement of blood parameters and serum biochemical parameters such as SGOT, SGPT, ALP and in vivo antioxidant parameters viz. SOD, CAT and LPO. Further, liver tissues were also subjected to histopathological analysis. The HPLC-DAD results showed the luteolin and quercetin 3-ß-d-glucoside as newly identified compounds in P. subpeltata species. Pre-treatment with acetone extract of P. subpeltata leaves at 200 and 400mg/kg doses significantly elevated the WBC, RBC and HB counts and retained the serum biochemical and enzymatic antioxidants levels to normal level. Based on this detailed study we conclude that acetone extract of P. subpeltata leaves offered better protection against hepatotoxicity induced by the acetaminophen.

Antidiabetic activity of Syzygium calophyllifolium in Streptozotocin-Nicotinamide induced Type-2 diabetic rats.

The study was initiated to determine the antidaibetic activity of Syzygium calophyllifolium in Streptozotocin-Nicotinamide (STZ-NA) induced diabetic rats. The rats were treated with 100 and 200mg/kg of the Syzygium calophyllifolium bark methanol extract (SCBM) and compared with the diabetic, normal and standard glibenclamide groups. The blood glucose level and body weight of the rats in different groups were monitored at regular intervals. The serum, blood biochemical and histopathological parameters of liver, kidney and pancreas were also analyzed. In vivo antioxidants like SOD, CAT, GST, GSH and GR levels were estimated in liver and kidney. SCBM (100mg/kg) extract could reduce the blood glucose level from the 15th day itself (213.67mg/dL) and the best reduction was observed till the end of the study with 259.25mg/dL (200mg/kg). Initial decrease in body weight was recovered after drug treatment and an increase in body weight was observed on the 4th week. The haematological parameters like total haemoglobin, packed cell volume percentage, total WBC and RBC content were found normal compared to that of normal untreated rats. Glibenclamide was also equally effective. The higher dose of SCBM extract could normalize the triglycerides, HDL, cholesterol and VLDL constituents in blood serum to the levels almost similar to that of normal rats. The results of the in vivo antioxidant levels showed that there are no significant difference in SOD, GSH and GR levels in all the groups compared to the normal control. SCBM and SMBM at 200mg/kg dose were much effective over the lower dose. The histology revealed that SCBM 200mg/kg could protect the cellular architecture of liver kidney and pancreas. The results from the study confirm ethnopharmacological significance of the plant and could be taken further for the development of an effective pharmaceutical drug against diabetes.