Comparison of the Efficacy of Corticosteroids With Enzymatic Agents in the Postoperative Sequelae for Lower Third Molar Surgery: A Prospective Study.

Introduction The presence of impacted third molars is a prevalent problem associated with varying degrees of difficulty in extraction and potential consequences, including pain, swelling, and trismus. According to studies, enzymatic combinations, such as bromelain, rutoside, trypsin, and serratiopeptidase, are known to have a very promising role in reducing inflammation and promoting wound healing. This study compared natural enzymatic agents with corticosteroids for postoperative pain, swelling, and trismus in the impacted lower third molar surgery. Objectives The present study aimed to compare the efficacy of prednisolone, a combination of trypsin, chymotrypsin, bromelain, rutoside, and papain, and serratiopeptidase in the postoperative sequelae after surgical extraction of impacted mandibular third molars. The primary objective was to assess the difference in swelling between the three groups. The secondary objectives were to assess the difference in postoperative pain and trismus between the three groups. Materials and methods A total of 150 patients who presented to the department of oral and maxillofacial surgery for surgical removal of an impacted mandibular third molar with a moderately difficult score of 5-7 in the Pederson difficulty index were chosen for a prospective study. Patients were categorized into three groups based on the postoperative drug prescribed. In group 1, prednisolone 10 mg was prescribed; in group 2, a combination of trypsin, chymotrypsin, bromelain, rutoside, and papain was prescribed; and in group 3, serratiopeptidase 15 mg was prescribed. All patients were prescribed a combination drug of aceclofenac 100 mg and paracetamol 325 mg twice daily as a standard analgesic. Swelling, pain, and trismus in each patient were recorded preoperatively and at postoperative day one and day seven. The Friedman test was employed to evaluate the variation in pain levels within the groups over time, while the Kruskal-Wallis test was utilized to investigate the disparity in pain levels between the groups. The difference in swelling and trismus within the groups across the timeline was measured by repeated measures analysis of variance (ANOVA), and the difference in swelling and trismus between the groups was measured by one-way ANOVA. A p-value below 0.05 was deemed to be statistically significant. Results Group 1 showed less swelling, pain, and trismus on both postoperative day one and day seven compared to group 2 and group 3, which was a statistically significant difference (P < 0.05). It was found that swelling, pain, and trismus measurements in postoperative day one and day seven in group 2 were comparatively less than in group 3. Neither group demonstrated any side effects or other complications during the follow-up period. Conclusion It can be concluded that the use of prednisolone postoperatively following surgical removal of the mandibular third molar provided better relief with regard to pain, trismus, and swelling compared to the enzymatic agents. Among enzymatic agents, a combination of trypsin, chymotrypsin, bromelain, rutoside, and papain was better in reducing pain, trismus, and swelling than serratiopeptidase drug.

Anti-inflammatory Role of Trypsin, Rutoside, and Bromelain Combination in Temporomandibular Joint Osteoarthritis: A Systematic Review.

The objective of this systematic review was to assess the effectiveness, acceptability, and safety of systemic enzyme therapy, consisting of trypsin, bromelain, and rutoside trihydrate, as an anti-inflammatory agent, either when utilized independently or in conjunction with non-steroidal anti-inflammatory drugs (NSAIDs). This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two studies met the inclusion criteria and were assessed in the review. The bias risk was evaluated using the risk-of-bias tool for randomized trials (RoB 2). Both studies revealed highly significant results for the study population. Individuals receiving oral enzymes and diclofenac sodium combination therapy showed a significant improvement in pain reduction, better eating, and mouth opening, as well as a decrease in joint noise and jerky mandibular motions. Patients receiving systemic enzyme therapy with diclofenac combinations performed better than those receiving NSAIDs alone, and the differences were quite substantial. For the treatment of internal derangement of the temporomandibular joint (TMJ), we recommend combining enzymes and diclofenac. Systemic enzyme therapy can be used in the treatment of TMJ osteoarthritis, as it shows a highly significant result in the study population.

Oral enzyme combination with bromelain, trypsin and the flavonoid rutoside reduces systemic inflammation and pain when used pre- and post-operatively in elective total hip replacement: a randomized exploratory placebo-controlled trial.

Background: Early mobilization after total hip replacement (THR) is key for fast recovery but is often limited by pain. Oral enzyme combinations (OECs) have demonstrated anti-inflammatory and pain-relieving effects. Objectives and design: This prospective, randomized, double-blind, placebo-controlled exploratory trial evaluated the effects of pre- and post-operative use of OEC (90 mg bromelain, 48 mg trypsin, 100 mg rutoside) following elective THR, on post-operative recovery. Methods: Candidates for primary elective cementless THR owing to osteoarthritis were eligible for participation [age ⩾50 years, body mass index 25-35 kg/m2, C-reactive protein (CRP) ⩽6 mg/L]. Following randomization to OEC or placebo, intervention started pre-operatively and continued onwards until day 42. Main outcomes included post-operative CRP levels (days 1-7), self-reported hip pain at rest (by 0-10 cm visual analogue scale on post-operative days 1-42), post-operative analgesic use [by cumulative analgesic consumption score (CACS) days 7-42], tolerability and adverse events. Results: Patients (N = 34) were recruited from a tertiary orthopaedic hospital in the Czech Republic, of whom 33 completed the study (OEC/placebo: n = 15/18). Baseline characteristics across the groups were comparable. Compared with placebo, the OEC group had numerically lower CRP levels on post-operative days 1-7, including peak level [mean (standard deviation) OEC versus placebo: 81.4 (28.3) versus 106.7 (63.3) mg/L], which translated into a significant 32% lower CRP area under the curve (p = 0.034). The OEC group reported significantly less pain during post-operative days 1-7 versus placebo (analysis of variance treatment × visit [F(4) = 3.989]; p = 0.005). Analgesic use was numerically reduced as assessed through an accumulated CACS. No deleterious effects on haemorheological parameters were observed in either group. Conclusions: Pre- and post-operative use of OEC significantly reduced CRP levels and patient self-reported pain. OEC may be an efficacious and safe treatment option to facilitate post-operative recovery following THR. Trial registration: EudraCT number 2016-003078-41.

Rutoside and Ascorbic Acid in the Treatment of Schamberg Pigmented Purpuric Dermatosis.

Schamberg disease is a type of pigmented purpuric dermatosis (PPD), which is a benign cutaneous capillaritis characterized by macules and patches most commonly found on the lower extremities. Rutoside and ascorbic acid have been shown in previous cases to be efficacious in the treatment of PPD lesions due to their free radical scavenging effect on capillaries. We present the case of a 19-year-old woman with Schamberg disease who achieved complete clearance of lesions within four months of daily rutoside and ascorbic acid treatment. The goal of this case report is to further demonstrate the effectiveness of this treatment and to call for investigation of its use as a standard of care in PPD.

Molecular interaction and cellular studies on combination photodynamic therapy with rutoside for melanoma A375 cancer cells: an in vitro study.

BACKGROUND: Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells. METHODS: For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured. RESULTS: The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside. CONCLUSION: The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.

Role of Oral Enzymes in Post Operative Septoplasty Cases.

Enzymes are complex macromolecules of amino acids which biocatalyse various body processes. The aim of this study is to evaluate the effect of oral enzymes for control of infection and inflammation in post operative septoplasty cases. 40 patients planned for septoplasty under general anaesthesia were taken up for study. 20 patients were included in group E and were given a combination of oral enzymes postoperatively. Remaining 20 patients were included in group D and were given diclofenac and paracetamol combination postoperatively. Patients were evaluated post operatively after 1, 2 and 4 weeks for post operative pain , swelling , congestion , patient satisfaction and other criterias. The results showed that pain and swelling was significantly less in oral enzymes group . There was less nasal obstruction , discharge and more patient satisfaction in enzyme group. There were less complications in enzyme group. So it can be concluded that oral enzymes are more effective for control of infection and inflammation in post operative septoplasty cases.

Anticonvulsive and behavior modulating effects of sophoretin and rutoside.

INTRODUCTION: Seizures are the hallmarks of most types of epilepsies. Behavioral and cognitive impairments coincide with interictal periods even though it is not clear whether these impairments spring out of the seizure itself or accompanying sociopsychological burden of the disease. MATERIALS AND METHODS: In this study, we investigated behavioral and cognitive consequences of a single GABA receptor-related seizure in mice, and examined the potential anticonvulsive and behavior-modulating properties of sophoretin (quercetin) and rutoside (rutin). RESULTS: The study demonstrated that sophoretin and rutoside, common flavonoids of the human diet, delay the seizure onset and reduce the seizure stage. Moreover, they exerted an antidepressant-like effect, which was independent of the seizure. Neither treatments nor seizure altered recognition and spatial memory performances of the mice. CONCLUSIONS: Behavioral or cognitive disturbances that are evident in epileptic patients did not appear following a single seizure. In addition, we suggest that both sophoretin and rutoside successfully alleviate the seizure severity without interfering in the behavioral stability and cognitive performance. Hence, these flavonoids may be of use as adjuncts to the current treatment options.

A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management.

INTRODUCTION: Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain. METHOD: The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups-oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical wounds after orthopedic surgery. RESULTS: A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR. CONCLUSION: TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent.

ETHNOPHARMACOLOGICAL RELEVANCE: Meadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions. MATERIALS AND METHODS: The characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis. RESULTS: FUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50µg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25µg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05). CONCLUSIONS: The observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts.

Content Determination of Chlorogenic Acid and Rutoside in Saussurea involucrate from Different Produc-ing Areas and Optimization of Decoction and Extraction Technology / 中国药房

OBJECTIVE:To detect the contents of chlorogenic acid and rutoside in Saussurea involucrate,and to optimize the decoction and extraction technology of S. involucrate from different producing areas. METHODS:The contents of chlorogenic acid and rutoside in 10 batches of S. involucrate from different producing areas were determined by HPLC. L9(34)orthogonal experiment was used to optimize the water amount,decoction times and decoction time using comprehensive score of extraction transport rate of chlorogenic acid and rutoside as index. The verification test was also conducted. RESULTS:The contents of chlorogenic acid and rutoside in 10 batches of S. involucrate were 0.380%-0.546% and 0.334%-0.617%;the optimal decoction technology was as follows as the amout of crude material of S. involucrate 100 g,soaking for 20 min,decocting for 3 times,12,10 and 10 fold of water,decocting 45,30 and 30 min,respectively. The extraction transfer rates of chlorogenic acid and rutoside were 96.2%(RSD=2.66%,n=3)and 89.3%(RSD=3.31%,n=3)in verification test. CONCLUSIONS:For S. involucrate from different producing areas,the contents of effective components are different;optimized decoction and extraction technology is stable and feasible.

The flavonoid 7-mono-O-(ß-hydroxyethyl)-rutoside is able to protect endothelial cells by a direct antioxidant effect.

The flavonoid 7-mono-O-(ß-hydroxyethyl)-rutoside (monoHER) is an effective protector against doxorubicin induced toxicity which has been related to the antioxidant activity of monoHER. The present study examines the potential relevance of the direct scavenging activity of the flavonoid. The potency of the direct antioxidant effect was confirmed by its instantaneous protection against intracellular oxidative stress in human umbilical vein endothelial cells at therapeutically achievable concentrations (EC50=60 nM) underpinning the involvement of a direct scavenging activity. This direct effect of monoHER is substantiated by (i) its site specific scavenging effect, i.e. on a molecular level monoHER is positioned at the location of radical formation, (ii) its position in the antioxidant network, i.e. on a biochemical level oxidized monoHER quickly reacts with ascorbate or glutathione, (iii) its location in the vascular system, i.e. on a cellular level monoHER is localized in the endothelial and smooth muscle cells in the vascular wall. It is concluded that the flavonoid monoHER can display a physiologically important direct antioxidant effect.

The cocoa flavanol (-)-epicatechin protects the cortisol response.

Various health benefits of the cocoa flavanol (-)-epicatechin (EC) have been attributed to its antioxidant and anti-inflammatory potency. In the present study we investigated whether EC is able to prevent deterioration of the anti-inflammatory effect of the glucocorticoid (GC) cortisol in the presence of oxidative stress. It was found that cortisol reduces inflammation in differentiated monocytes. Oxidative stress extinguishes the anti-inflammatory effect of cortisol, leading to cortisol resistance. EC reduces intracellular oxidative stress as well as the development of cortisol resistance. This further deciphers the enigmatic mechanism of EC by which it exerts its anti-inflammatory and antioxidant action. The observed effect of the cocoa flavanol EC will especially be of relevance in pathophysiological conditions with increased oxidative stress and consequential GC resistance and provides a fundament for the rational use of dietary antioxidants.

Protective effects and mechanism of Rutoside on lung injury during experimental acute pancreatitis / 中国药理学通报

Aim To investigate effects and the mechanism of rutoside (Ru) on lung injury during experimental acute pancreatitis (AP) . Methods The model of AP was induced by retrograde injection of Sodium Taurocholate(STC)into biliopancreatic duct in rat. Ru (15,30,60 mg?kg -1 ?h -1 ) was administered by intravenous infusion for 6 hours immediately after the induction of AP. Indexes of blood gas analysis, the wet/dry lung ratio and pathological changes of lung tissue were observed and we also measured levels of TNF-?, ICAM-1and NF-?B. Result Ru(60 mg?kg -1 )increased the arterial PO_2, which decreased in AP rats. Ru (30,60 mg?kg -1 ) could decrease the wet/dry lung ratio, and improve pathological changes of lung tissue. Ru(15,30,60 mg?kg -1 ) could decrease levels of TNF-?, ICAM-1, and NF-?B. Conclusion The study indicates that Ru administered by intravenous infusion exerts certain protective effects on lung injury in experimental AP rats by decreasing levels of TNF-?, ICAM-1 and NF-?B.

The effect of rutoside on blood rheology in murine acute pancreatitis / 中国药理学通报

AIM To study the effect of rutoside (Ru) on blood rheology in murine acute pancreatitis (AP). METHODS Blood rheology, enzymatic levels and pathology of the pancreas were evaluated in all Wistar rats. The pancreatic sections were scored and compared. RESULTS In AP group, the whole blood viscosity, the plasma viscosity, the eryrocyte sedimentation, the hematocrit, the agglutinatin index of red blood cell, and the rigidity index were significantly elevated. The pancreatitis injury was described as evident pancreatic acinar necrosis and infiltration of inflammatory cells. Ru 120, 60, 30 mg?kg -1 (sc) ameliorated the abovementioned adverse pathophysiological changes seen in the control group. CONCLUSION During the course of AP, rutoside ameliorated the blood rheology abnormality and showed a protective effect on pancreatic tissue.

Effect of Rutoside on pancreatic acinar cell apoptosis in rats with acute pancreatitis and its mechanism / 中国药理学通报

Aim To study the effect of Rutoside (Ru) on pancreatic acinar cell apoptosis in rats with acute pancreatitis(AP). Methods The AP model in rats was induced by retrograde injection of 3% sodium taurocholate into biliopancreatic duct. Ru (15, 30 and 60 mg?kg~ -1 ?h~ -1 )was administered by intravenous infusion for 6 hours immediately after the induction of AP.The histopathological changes of pancreas were observed under light microscope and electronic microscope.A terminal deoxynucleotidyl transferase-mediated dUTP-biotion nick end labeling(TUNEL) method was used to detect apotosis of pancreatic acinar cell and apoptosis immunohistochemical method. Results Ru (15, 30 and 60 mg?kg~ -1 ?h~ -1 ) improved the histopathological changes of pancreas significantly.The apotosis index of pancreatic acinar cells was significantly higher than that the AP model group. The gray value of Fas was lower than that of the AP model group. Immuno-staining revealed that moderate to strong FasL immunoreactivity was present in the cytoplasm of the acini of all groups.But in AP model group,the gray value of FasL was lower than that in Ru-treated groups.AI was positively correlated with the gray value of Fas,and was negatively correlated with the gray value of FasL and the severity of pancreas damages. Conclusion The protective effect of Ru on AP may be concerned with the induction of apoptosis in injured pancreatic acinar cells.And the Fas/FasL system may contribute to the process.