Natural Drug
Objective
Annona tomentosa R.E.Fr is a species not endemic to Brazil that belongs to the phytogeographic areas of the Amazon, Cerrado and Pantanal. Popularly known as “araticum rasteiro” or “araticum de moita”, A. tomentosa is edible and tea made from the leaves has been used as an anti-inflammatory by native communities. There is no scientific evidence for these uses of A. tomentosa, especially those related to the control of pain and inflammation. For this reason, in the present study we evaluated the antinociceptive and anti-inflammatory activities of partitions from the methanolic extract of A. tomentosa leaves (A. tomentosa leaf methanolic extract (ATFM) in hexane partition: ATFM-H; ATFM in dichloromethane partition: ATFM-D; ATFM in ethyl acetate partition: ATFM-Ac; ATFM in butanol partition: ATFM-B) in mice.
Methods
The antinociceptive effects of leaf extracts from A. tomentosa were evaluated by abdominal writhing and tail-flick tests, while the anti-inflammatory effects were evaluated by paw oedema and air-pouch tests. The locomotor activity was evaluated with the open-field test. Furthermore, we evaluated the possible action mechanism of A. tomentosa, using naloxone, nitro-L-arginine methyl ester, glibenclamide, atropine, naltrindole and norbinaltorphimine in tail-flick tests. The productions of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β were also evaluated.
Results
The chromatographic fractionation of the partitions of the methanolic extract from the leaves of A. tomentosa revealed the presence of diterpenes, flavonoids, and steroids compounds. From the analysis of the hexane partition kaurenoic acid was identified as the major component. ATFM-H and ATFM-D had a significant antinociceptive effect in acute pain models in mice. The ATFM-H showed central antinociceptive effect from the involvement of the δ opioid receptors, without causing alterations in the locomotor activity of the mice, while ATFM-D was effective in decreasing paw oedema and TNF-α and IL-1β production.
Conclusion
These results demonstrate that leaf extracts from A. tomentosa present antinociceptive and anti-inflammatory effects that can to be used in relieving algesic and inflammatory conditions.
Background
Amiodarone is a useful antiarrhythmic drug. Phlebitis, caused by intravenous amiodarone, is common in patients in coronary care units (CCUs).
The aim of this study was to evaluate the effect of topical chamomile on the incidence of phlebitis due to the administration of an amiodarone infusion into the peripheral vein.
Design, Setting, Participants and Interventions
This was a randomized, double-blind clinical trial, conducted on 40 patients (n = 20 per group) in two groups—an intervention group (chamomile ointment) and a control group (lanoline, as a placebo), hospitalized in the CCUs and undergoing an amiodarone infusion into the peripheral vein over 24 h. Following the cannulation and commencement of the infusion, placebo or chamomile ointment was rubbed in, up to 10 cm superior to the catheter and repeated every eight hours for three days. The cannula site was then assessed based on the phlebitis checklist.
Main Outcome Measures
The incidence and time of occurrence of phlebitis, relative risk, severity of phlebitis were the main outcome measures.
Nineteen patients (19/20) in the control group had phlebitis on the first day of the study and one patient (20/20) on the second day. In the intervention group, phlebitis occurred in 13 cases (13/20) on the first day and another two (2/7) was found on the second day. The incidence of phlebitis was significantly different between two groups (P = 0.023). The cumulative incidence of phlebitis in the intervention group (15/20) is significantly later and lower than that in the control group (20/20) during two days (P = 0.008). Two patients in the intervention group did not develop phlebitis at all during the 3-day study. Also, the relative risk of phlebitis in the two groups was 0.68 (P = 0.008 5). A significant difference was not observed with regard to phlebitis severity in both groups.
It seems that phlebitis occurred to a lesser extent and at a later time frame in the intervention group compared to control group. Topical chamomile may be effective in decreasing the incidence of phlebitis due to an amiodarone infusion.
Trial Registration
This protocol was registered in the Iranian Registry of Clinical Trials (IRCT2014042017361N1).
Rheum ribes L. is a plant native to China, Iran, Turkey, India, and a few other countries. Antidiarrheal activity is considered to be one of its important properties according to various systems of traditional medicine. An increasing rate of bacterial resistance to antibiotics has led to treatment failure in some cases of shigellosis in children, and underlines a need for safe, efficient and valid options.
The purpose of this study is to evaluate the efficacy of R. ribes syrup as a complementary medicine for treatment of shigellosis in children.
This randomized, double-blind, placebo-controlled trial started with a group of 150 children aged between 12-72 months with suspected Shigella dysentery. R. ribes syrup or placebo syrup was administered to the intervention and control groups, respectively for 5 days. In addition, the standard antibiotic treatment (ceftriaxone for the first 3 days and cefixime syrup for 2 further days) was administered to both groups.
Body temperature, abdominal pain, need for antipyretics, defecation frequency, stool volume and consistency and microscopic stool examination were recorded as outcome measures. Any observed adverse effects were also recorded.
Mean duration of fever and diarrhea in the R. ribes group was significantly lower than that in the placebo group (P = 0.016 and 0.001, respectively). In addition, patients in the R. ribes group showed shorter duration of need for antipyretics and shorter duration of abdominal pain (P = 0.012 and 0.001, respectively). However, there were no significant differences between the two groups regarding the microscopic stool analyses. Furthermore, no adverse effect was reported.
R. ribes syrup can be recommended as a complementary treatment for children with Shigella dysentery.
Iranian Registry of Clinical Trial: IRCT2014070518356N1.
Different parts of Murraya paniculata have been used traditionally for treating several ailments including mental disorders. The present study was designed to evaluate the antianxiety and antidepressant potential of M. paniculata leaves using elevated plus maze model and forced swim test, respectively.
Extracts of M. paniculata made with petroleum ether (60-80 °C), chloroform, ethanol and water were evaluated for antianxiety and antidepressant activity. The anxiolytic chloroform extract was subjected to column chromatography, yielding five fractions (F1-F5). Fraction F5 (100 mg/kg), which showed notable anxiolytic activity, was further chromatographed to get four subfractions (F5.1-F5.4). Simultaneously, the ethanol extract was partitioned with ethyl acetate to obtain ethyl acetate soluble fraction (EASF) and ethyl acetate insoluble fraction. Phytochemical screening of bioactive extracts/fractions and detection of mahanimbine in M. paniculata leaf extract by thin-layer chromatography was also carried out.
Fraction F5.3 (25 mg/kg) and EASF (20 mg/kg) showed significant anxiolytic and antidepressant activity, respectively. Thin-layer chromatography and phytochemical screening demonstrated the absence of mahanimbine in M. paniculata leaves. Coumarins were observed to be responsible for the anxiolytic activity.
The results validate the traditional use of M. paniculata leaves in the treatment of mental disorders.
To investigate the antioxidant activities as well as phytochemical constituents of Antidesma thwaitesianum Müll. Arg. leaf extracts.
The leaves of A. thwaitesianum were extracted using three different methods: blending with distilled water, maceration with ethanol and decoction. The chemical antioxidant activity of the plant leaf extracts was evaluated using 2,2-diphenyl-1-picryhydrazyl (DPPH) radical and 2,2′-azinobis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS+) radical scavenging assays, as well as the ferric reducing antioxidant power assay. Cellular antioxidant activity was determined by superoxide and nitric oxide scavenging assays. The cytotoxicity of the leaf extracts in RAW 264.7 and differentiated HL-60 cells was tested in parallel using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays, respectively. The total phenolic and flavonoid contents were also assessed by spectrophotometric analysis. Phytochemical constituents of the most potent extract were investigated by liquid chromatography with an electrospray ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF-MS/MS).
The ethanolic (ME) and decoction (LW) extracts of dried leaves had the highest chemical scavenging activity against DPPH and ABTS+ free radicals with half maximal effective concentration (EC50) values ranging from 3.54 to 6.44 μg/mL. ME and LW exerted moderate ferric reducing activity, with ferric reducing antioxidant power values of 847.41 and 941.26 mg Fe2+/g extract, respectively. Similarly, ME showed potent cellular scavenging activity against superoxide and nitric oxide radicals with EC50 values of 58.12 and 71.90 μg/mL, respectively. However, LW exhibited only strong nitric oxide scavenging activity with an EC50 value of 91.20 μg/mL. The cell viability of RAW 264.7 and HL-60 cells was greater than 70% in all tested concentrations of both extracts, thus confirming the absence of their cytotoxicity. ME and LW contained high total phenolic contents of 231.14 and 274.42 mg gallic acid equivalents per gram, respectively, as well as high total flavonoid contents of 18.82 and 22.17 mg quercetin equivalents per gram, respectively. LC-ESI-QTOF-MS/MS analysis revealed the presence of 52 structurally characterized compounds in ME, 43 of which were tentatively identified. Hydroxycinnamic acids such as caffeic acid and its derivatives were the predominant phenolic compounds.
This is the first report describing potent chemical and cellular antioxidant effects of the ethanolic leaf extract of A. thwaitesianum. The extract contained high total phenolic and flavonoid contents. LC-ESI-QTOF-MS/MS analysis further revealed an abundance of caffeic acid derivatives and flavonoids. These data support its potential use as dietary supplements in oxidative stress prevention.
Diabetes mellitus (DM) is known to be associated with increase of oxidative stress products. The direction of effect of any treatment on these products could therefore be a reliable measure of its efficacy on DM. So the aim of this study was to investigate the activity of insulin, Ocimum gratissimum L. (OG) and Vernonia amygdalina L. (VA) on oxidative stress products.
Thirty-six female Wistar rats weighing 150-200 g were randomly divided into six groups of six rats each. Thirty rats were induced for type 1 DM (DM1) with a single intraperitoneal administration of 65 mg/kg body weight of streptozotocin. Group 1 was normal control and was administered distilled water while Group 2 served as DM1 control group; Groups 3, 4, 5 and 6 were diabetic rats treated with 208 mg/kg OG (DM1 + OG), 52 mg/kg VA (DM1 + VA), 208 mg/kg OG + 52 mg/kg VA (DM1+OG +VA) and 0.16 IU insulin (DM1 + insulin) respectively. Determination of methemoglobin and sulfhemoglobin was achieved by the absorption spectrum principle. Red blood cell (RBC) catalase was assayed by continuous spectrophotometric method.
The RBC catalase concentration was significantly decreased in the DM1 and DM1+VA groups when compared with the normal control. DM1 + OG significantly increased RBC-catalase when compared to DM1. The methemoglobin concentration was significantly reduced in the DM1, DM1 + VA, DM1 + OG + VA and DM1 + insulin groups when compared to the normal control group. The sulfhemoglobin concentration was significantly increased in the diabetic control and the diabetic treated groups when compared to the normal control. DM1 + OG reduced the sulfhemoglobin concentration when compared to DM1. The blood glucose concentration of all the diabetic groups was significantly raised compared to normal control. OG, VA and insulin significantly reduced the blood glucose concentration with the efficacy of OG and VA higher than insulin.
Adverse alteration of oxidative indices were observed in type 1 DM model. Treatment with OG and insulin showed potent antioxidant activity, while the hypoglycemic efficacy of OG and VA were higher than insulin.
Dysmenorrhea is a common gynecologic problem. In some cases, non-medical treatments are considered to be more effective, with fewer side effects. Ginger and exercise are alternative treatments for dysmenorrhea, but in the present study they were not combined.
In this study, the effects of ginger and exercise on primary dysmenorrhea were compared.
This randomized controlled trial was performed in Mazandaran University of Medical Sciences, Iran. Two groups of female students were recruited by simple random allocation. In each group, 61 students with moderate to severe primary dysmenorrhea with regular menstrual cycles and without a history of regular exercise were assessed. The ginger group received 250 mg ginger capsules from the onset of menstruation. In the exercise group, belly and pelvic stretching exercises were performed for 10 min, 3 times per week.
Intensity of pain was assessed according to a visual analogue scale after the first and the second month.
Exercise was significantly more effective than ginger for pain relief (31.57 ± 16.03 vs 38.19 ± 20.47, P = 0.02), severity of dysmenorrhea (63.9% vs 44.3% mild dysmenorrhea, P = 0.02) and decrease in menstrual duration (6.08 ± 1.22 vs 6.67 ± 1.24, P = 0.006), in the second cycle.
Stretching exercises, as a safe and low-cost treatment, are more effective than ginger for pain relief in primary dysmenorrhea.
Trial registration
The trial was registered in www.IRCT.ir with No. 201203118822N2.
Geophila repens (L.) I. M. Johnst. (Rubiaceae), a small, creeping, perennial herb, is claimed to have memory-enhancing property. The goal of this study was to assess its antioxidant and anticholinesterase activity and conduct a rapid bioautographic enzyme assay for screening acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition of G. repens extracts.
Antioxidant activity of G. repens extracts was assessed by performing 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide (SOD), hydroxyl (OH) and total antioxidant capacity (TAC) assays. Anticholinesterase activity was investigated by quantifying the AChE and BChE inhibitory activities of chloroform (CGR), ethyl acetate (EGR) and methanol (MGR) extract fractions from G. repens leaves. A rapid high-performance thin-layer chromatography (HPTLC) bioautographic method for the detection of AChE and BChE inhibition was performed.
Among all extract fractions, EGR exhibited the highest half maximal inhibitory concentration (IC50) in DPPH, SOD, NO, OH and TAC assays, with IC50 of (38.33 ± 3.21), (45.14 ± 1.78), (59.81 ± 1.32), (39.45 ± 0.79) and (43.76 ± 0.81) μg/mL respectively. EGR displayed competitive, reversible inhibition of AChE and BChE activities with IC50 of (68.63 ± 0.45) and (59.45 ± 0.45) μg/mL, respectively. Total phenolic and flavonoids contents of EGR were found to be 360.42 mg gallic acid equivalents and 257.31 mg quercetin equivalents per gram of extract. Phytoconstituents of the EGR extract that were inhibitors of cholinesterase produced white spots on the yellow background of HPTLC plates in the bioautographic test.
The results of this study revealed that phenols and flavonoids could be responsible for the antioxidant, anticholinesterase activities of G. repens.
The fatality of cancer is mostly dependent on the possibility of occurrence of metastasis. Thus, if the development of metastasis can be prevented through novel therapeutic strategies targeted against this process, then the success of cancer treatment will drastically increase. In this study, therefore, we evaluated the antimetastatic potentials of an extract of Khaya senegalensis and curcumin on the metastatic liver cell line HepG2, and also assessed the anticancer property of the extract.
Cells were cultured and treated with graded concentrations of test substances for 24, 48, or 72 h with provisions made for negative controls. Treated cells were assessed as follows: nanotechnologically—atomic force microscopy (AFM) was used to determine cell stiffness; biochemically—cell cytotoxicity, glutathione level and adenosine triphosphate status, caspase activation and mitochondrial toxicity were considered; and microbiologically—a carrot disk assay was used to assess the anticancer property of the extract of K. senegalensis.
Curcumin and K. senegalensis increased the cell stiffness by 2.6- and 4.0-fold respectively, indicating their antimetastatic effects. Corresponding changes in redox (glutathione level) and energy (adenosine triphosphate) status of the cells were also demonstrated. Further mechanistic studies indicated that curcumin was not mitotoxic in HepG2 cells unlike the K. senegalensis extract. In addition, the extract potently inhibited the Agrobacterium tumefaciens-induced genetic transformation based on carrot disk assay.
Cell elasticity measurement data, using AFM, strongly suggested, for the first time, that both curcumin and the extract of K. senegalensis exhibited antimetastatic properties on HepG2 cells.
To evaluate the effects of homoeopathic ultrahigh dilutions of Aconitum napellus in Baker's yeast-induced fever in rabbits.
Rabbits were divided into 4 groups and each group contained 6 rabbits. Baker's yeast suspension (20%) was injected subcutaneously. After fever induction, paracetamol and homoeopathic ultrahigh dilutions (A. napellus 200c and 1 000c) were given orally. Rectal temperature was measured with digital thermometer hourly.
Fever was induced in all the rabbits after 4 hours of Baker's yeast administration. A. napellus 200c and 1000c significantly reduced the temperature (P > 0.05). In positive control, temperature decrease was more significant (P > 0.001).
The above findings indicate the effectiveness of ultrahigh dilutions of A. napellus in Baker's yeast-induced fever in rabbits. However, the effects were slower and less significant than standard medicine. Moreover, future research is required to know their mechanism of reducing temperature.
Acute diarrhea is one of the major illnesses that cause death in children, despite clinical interventions and the use of oral rehydration therapy. Thus, there is need to discover other effective, affordable and accessible treatments for this disease. Therefore, this study was carried out to investigate the effects of hexane extract of Citrus limon peel (HECLP) on castor oil-induced diarrhea in rats.
Diarrhea was induced in male albino Wistar rats weighing 100-150 g. The antidiarrheal activity of HECLP at different oral dosages (5, 10 and 20 mg/kg) was investigated by counting the number of wet fecal pellets. Animals were further treated with propranolol, prazosin, nifedipine and atropine to assess the effects of receptor blockers on the activities of the extract. The effects of HECLP on castor oil-induced enteropooling and the intestinal transit time of activated charcoal were also evaluated.
Each of the 3 doses of C. limon significantly reduced (P < 0.05) the number of wet fecal pellets produced by animals, with 20 mg/kg HECLP producing the highest percentage inhibition (34.2%). Wet fecal pellet inhibition by the standard drug loperamide (3 mg/kg p.o.) was 68.4% relative to the negative control. Blockage of β adrenergic receptors by propanolol abolished the antidiarrheal effects of HECLP. Intestinal fluid accumulation was inhibited by 68.7% and 78.5% by 20 mg/kg HECLP and loperamide respectively. Furthermore, 20 mg/kg HECLP significantly (P < 0.05) reduced the percentage intestinal transit time (21.4% ± 1.42%), relative to the control (34.2% ± 4.29%); atropine (5 mg/kg, intraperitoneal injection) significantly (P < 0.001) reduced the percentage intestinal transit time to 11.2% ± 0.85%.
These results suggest that C. limon peel possesses antidiarrheal effects through antisecretory and antimotility mechanisms that act through the β adrenergic system.
To evaluate the effects of Zingiber cassumunar (Plai cream) in either 7% or 14% concentration on delayed onset muscle soreness (DOMS).
Seventy-five untrained healthy volunteers (28 males and 47 females), performed 4 sets of 25 eccentric repetitions of the dominant quadriceps muscle on an isokinetic dynamometry machine. Participants were then randomized into 3 groups: 14% Plai cream, 7% Plai cream and placebo cream. Two grams of the cream (strips of 5-cm long) were gently rubbed into the quadriceps muscles for 5 min immediately following the exercise and every 8 h thereafter for 7 d in all groups. Muscle soreness, muscle strength, jump height, thigh circumference and creatine kinase were measured before and after eccentric exercise.
Compared to the placebo cream the 14% Plai cream substantially reduced muscle soreness over the 7 d by -82% (95% CI = -155% to -6%, P = 0.03), but had similar muscle soreness effects to 7% Plai cream (-34%, -96% to 27%, P = 0.2). Compared to the placebo cream the 7% Plai cream resulted in a small non-significant reduction in muscle soreness levels over the following 7 d (-40%, -116% to 36%, P = 0.3). Compared to placebo cream there was little effect of Plai cream (7% or 14%) on muscle strength, jump height, thigh circumference or creatine kinase concentration.
Using 14% Plai cream over a 7-day period substantially reduced muscle soreness symptoms compared to 7% Plai cream or a placebo cream. The authors suggest that the administration of 14% Plai cream is a useful alternative in the management of DOMS.
Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema.
A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation.
Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Resultsfrom the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively.
Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.
Ayurvedic formulations are preferred over other formulations as well as commercialized on broad level to treat various ailments. The World Health Organization has established certain guidelines for quality control of heavy metals and pesticide residues. Bacopa monnieri, a popular herb with immunomodulator and memory-enhancing properties is the chief constituent of several Ayurvedic formulations, which include Brahmi Vati (BV), Brahmi Ghrita (BG) and Saraswat Churna (SC), etc. In view of the World Health Organization guidelines, two products of each formulation from six different manufacturers were purchased from Ayurvedic Pharmacy, Bulanala-Varanasi, India for testing heavy metal and pesticide residue.
In the present study, all the formulations—BV, BG and SC—were selected for estimation of four heavy metals namely lead (Pb), cadmium (Cd), chromium (Cr) and nickel (Ni) by a plasma emission spectrophotometer. Organochlorine pesticidal residues were estimated for dichlorodiphenyl trichloroethane, isomers of hexachlorocyclohexane (HCH) and α-endosulfan, etc. in total 12 samples of test formulations containing Bacopa monnieri L. using gas chromatography technique.
Out of 12 samples, Pb, Cd, Cr and Ni were present in all samples but below the permissible limit. Although atrazine, aldrin, dialdrin were in below detection limit, but other pesticides were detected in some samples as oxamyl, hexachlorocyclohexanes (α-HCH, β-HCH and γ-HCH), dichlorodiphenyl trichloroethane and dichlorodiphenyl dichloroethylene.
The presence of heavy metals in the formulations was low to cause toxicity. However evaluation of heavy metals and pesticide residue in every batch is necessary.
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