Research progress on chemical constituents of Rhododendron molle and its pharmacological activities / 中草药

Rhododendron molle is a plant of the Ericaceae family. It is commonly used in the treatment of rheumatoid arthritis. Modern pharmacological studies have confirmed that its diterpenoids are main medicinal ingredients with anti-inflammatory, analgesic and other pharmacological effects. Through reviewing domestic and foreign literatures, this review aims to provide a comprehensive overview of the research progress in the chemical constituents and pharmacological effects of R. molle, and briefly prospects research of the titled plant.

Anti-inflammatory and anti-nociceptive activities of essential oil of Waltheria indica / Actividades antiinflamatorias y nociceptivas del aceite esencial de Waltheria indica

This paper reports for the first time volatile compounds, anti-nociceptive and anti-inflammatory activities of essential oils from the leaves of Waltheria indica L. (Stericullaceae) growing in Nigeria. The essential oil was hydro-distilled and characterized by gas chromatography-flame ionization detection (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS) analyses. The anti-inflammatory activity was evaluated on carrageenan induced rat paw edema while the anti-nociceptive test was based on hot plate model. The hydro-distillation afforded 0.41% (dry weight basis) of light green oil. Forty compounds representing 99.8% were identified in the oil. The main constituents of the oil were limonene (34.7%), sabinene (21.2%) and citronellal (9.7%). The anti-nociceptive property of the essential oils statically inhibited edema development (p<0.001) at a dose of 200 and 400 mg/kg independent of time of exposure. However, the 100 mg/kg Waltheria indica essential oils (WIEO) displayed a relatively low inhibition (p<0.01-p>0.5) which declines as exposure time increases. The anti-inflammatory activities shows a steady rate and non-dose dependent activity (p<0.001) up to the 3rd h of inflammation study. Conversely, a sharp reduction at the rate of p<0.5, 0.1 and 0.01 for the 100, 200 and 400 mg/kg WIEO doses respectively. Overall, the results presented sustain and establish the anti-nociceptive and anti-inflammatory properties and justifies the need for further evaluation and development of the essential oils from this plant.

Este artículo informa por primera vez de compuestos volátiles, actividades anti-nociceptivas y antiinflamatorias de aceites esenciales de las hojas de Waltheria indica L. (Stericullaceae) que crecen en Nigeria. El aceite esencial fue hidro-destilado y se caracterizó por cromatografía de gases-detección de ionización de llama (GC-FID) y cromatografía de gases junto con análisis de espectrometría de masas (GC-MS). La actividad antiinflamatoria se evaluó en el edema de pata de rata inducido por carragenano, mientras que la prueba antinociceptiva se basó en el modelo de placa caliente. La destilación hidráulica proporcionó 0,41% (en peso seco) de aceite verde claro. Cuarenta compuestos que representan el 99.8% fueron identificados en el aceite. Los principales componentes del aceite fueron el limoneno (34,7%), el sabineno (21,2%) y el citronelal (9,7%). La propiedad anti-nociceptiva de los aceites esenciales inhibió estáticamente el desarrollo del edema (p<0.001) a una dosis de 200 y 400 mg/kg independientemente del tiempo de exposición. Sin embargo, los aceites esenciales de Waltheria indica de 100 mg/kg (WIEO) mostraron una inhibición relativamente baja (p<0.01-p>0.5) que disminuye a medida que aumenta el tiempo de exposición. Las actividades antiinflamatorias muestran una tasa constante y una actividad no dependiente de la dosis (p<0.001) hasta la tercera hora del estudio de inflamación. Por el contrario, una fuerte reducción a una tasa de p<0.5, 0.1 y 0.01 para las dosis de 100, 200 y 400 mg/kg de WIEO respectivamente. En general, los resultados presentados sostienen y establecen las propiedades anti-nociceptivas y antiinflamatorias y justifican la necesidad de una mayor evaluación y desarrollo de los aceites esenciales de esta planta.

Anti-nociceptive effect of seed extract of Acacia tortilis in rodents

Background: Management of pain is a primary clinical concern for any pathology in medical field. Addiction liability of opioids and troublesome gastrointestinal side effects of NSAIDs leads to intensive research for compound with lesser side effects.The aim of the study to evaluate the anti-nociceptive activity of Acacia Tortilis Seed Extract (ATE) in experimental animals.Methods: First of all, animals were randomly allocated into four groups of six animals each. In acetic acid induced writhing test model, Group I (NC) served as vehicle control received saline/Tween 80 0.1%, 10ml/kg BW orally, group II (ATE-100) and III (ATE-200) received ATE in dose of 100 and 200mg/kg BW orally respectively and group IV received the standard drug diclofenac sodium in dose of 50 mg/kg BW orally. Group I to IV were same in rest of three experimental models. One additional group of standard drugs (group V) morphine sulfate in dose of 5 mg/kg BW subcutaneously (SC) was allocated for screening method hot plate and tail flick tests. In Formalin induced paw licking test, three additional groups (group V) morphine sulfate in dose of 5mg/kg BW SC, group VI- morphine+naloxone (5mg/kg SC +2mg/kg intra-peritoneally (IP) and group VII - ATE+ naloxone (200mg/kg BW orally +2mg/kg BW IP) were also made.Results: The ATE when administered orally in dose of 100 and 200mg/ kg body weight (BW), produced significant analgesic activity (P <0.01) in acetic acid induced writhing syndrome and late phase of formalin test. In the hot plate test in mice and tail flick test in rats, ATE in same doses also showed significant analgesic activity (P <0.05) which is almost equally efficacious to standard drug diclofenac sodium (50mg/kg BW orally) but far less efficacious than morphine sulfate (5mg/kg BW subcutaneous).ATE (200mg/Kg BW orally) activity did not blocked by naloxone (2mg/kg intra-peritoneal).Conclusions: ATE possesss significant anti-nociceptive activity as evidenced in all the animal models of nociception. It might exert its effect through the peripheral mechanism of analgesic action possibly by interference in biosynthesis, release and/or action of prostaglandins and leukotrienes.

Beneficial effects of methanolic extract of Indigofera linnaei Ali. on the inflammatory and nociceptive responses in rodent models

ABSTRACT Indigofera linnaei Ali. (Tamil Name: Cheppu Nerinjil) belongs to the family Fabaceae, used for the treatment of various ailments in the traditional system of medicine. In the present study, the beneficial effects of methanol extract of whole plant of I. linnaei (MEIL) were evaluated on inflammation and nociception responses in rodent models. In vitro nitric oxide (NO), lipoxygenase (LOX) and cyclooxygense (COX) inhibitory activities were also performed to understand the mode of action. MEIL at the dose of 200 & 400 mg/kg, p.o. significantly inhibited carrageenan induced rat paw volume and reduced the weight of granuloma in cotton pellet granuloma model. The results obtained were comparable with the standard drug aceclofenac. The anti-nociceptive effect of MEIL in mice was evaluated in hot plate and acetic acid induced writhing model. The plant extract significantly reduced the number of writhes and the analgesic effect was higher than that of the standard drug aspirin. However, the extract fails to increase the latency period in hot plate method suggesting that the extract produce nociception by peripheral activity. The extract produced inhibitory effect on NO, LOX and COX in concentration dependent manner. The extract exhibited pronounced and selective COX-2 inhibition. Altogether, these results suggested that the methanol extract of Indigofera linnaei could be considered as a potential anti-inflammatory and analgesic agent.

RESUMO Indigofera linnaei Ali pertence à família Leguminosae e é utilizada para o tratamento de várias doenças na medicina tradicional. No presente estudo, os efeitos benéficos do extrato metanólico da planta inteira de I. linnaei (MEIL) foram avaliados em respostas inflamatórias e nocicepção em modelos de roedores. Testes in vitro de atividade inibitória do óxido nítrico (NO), lipoxigenase (LOX) e ciclooxigenase (COX) também foram realizados para compreender o modo de ação. MEIL nas doses de 200 e 400 mg/kg, p.o. inibiu significativamente o volume da pata de rato induzido por carragenana e reduziu o peso do granuloma no modelo de pélete de algodão. Os resultados obtidos foram comparáveis ao do fármaco padrão, aceclofenaco. O efeito anti-nociceptivo de MEIL foi avaliado em camundongos no modelo de placa quente e de contorção induzida por ácido acético. O extrato da planta reduziu significativamente o número de contorções e o efeito analgésico foi maior do que o do fármaco padrão, ácido acetilsalicílico. Porém, o extrato não conseguiu aumentar o período de latência no método da placa quente, sugerindo que este produz nocicepção por atividade periférica. O extrato produziu efeito inibitório sobre o NO, LOX e COX dependente da concentração. O extrato exibiu inibição acentuada e seletiva da COX-2. No seu conjunto, estes resultados sugerem que o extrato metanólico de Indigofera linnaei poderia ser considerado como agente anti-inflamatório e analgésico potencial.

Evaluation of Antinociceptive Activity of Methanol Extract from Cleome rutidosperma in Mice / 中草药·英文版

Objective Cleome rutidosperma (Capparidaceae), commonly known as “Fringed Spider Flower”, is a medicinal plant found in Southeast Asia. C. rutidosperma is used in folk medicine for diuretic, laxative, analgesic, anti-inflammatory, antipyretic, antimicrobial, anti-oxidant, hypoglycemic, and anthelmintic activities. We have evaluated the anti-nociceptive properties of methanol extract from C. rutidosperma (MECR) in vivo. Methods Thermal method (hot plate test and tail flick test) was induced to judge the anti-inflammatory effect and couple of chemical method also used (formalin induced licking test; writhing test carried by acetic acid) to evaluate analgesic effect. Both of these tests were made over animal models, like mice and rats. Two different doses (100 and 200 mg/kg) were used for each case of test, while morphine sulphate (5mg/kg, ip) was used as reference drug. Results MECR demonstrated the significantly anti-nociceptive activity in the analgesic and anti-inflammatory tests by reducing nociception in mice models (P < 0.001). In the hot-plate and tail-flick tests, MECR significantly elongated the time to response to the thermal stimuli (100 and 200 mg/kg with P < 0.05, 0.001). The remarkable increase in the latency was observed at 90 and 120 min. In acetic acid-induced writhing test and formalin induced licking test for anti-inflammatory activity, MECR at 100 and 200 mg/kg doses exhibited significant (P < 0.001) reduction of writhing and licking response. Conclusion The anti-inflammatory and analgesic effects of C. rutidosperma propose that this effect may be a result of both peripheral and central mechanisms. Further study is required to ensure the proper mechanism of action as well as the active ingredient.

Investigation of centrally and peripherally acting analgesic and anti-infl ammatory activity of biological immune response modulator (an Amazonian plant extract) in animal models of pain and infl ammation.

Background: Biological immune response modulator (BIRM) - An aqueous extract of dried roots of the species dulcamara (family Solanaceae) grown in Ecuador, considered as a natural remedy for various disease is promoted as a natural herbal medicine. Our aim of the study was to assess the central and peripheral analgesic and anti-infl ammatory property of BIRM and to study its mechanism of action. Methods: Peripheral analgesic and anti-infl ammatory activity was evaluated using acetic acid induced writhing test and carrageenan paw edema test in male Swiss Albino mice (n=8 per group). Formalin test was taken up to evaluate BIRM’s centrally, as well as peripheral antinociceptive action. Results: We observed through our studies that BIRM when administered repeatedly for 7 days (4 ml/kg, p.o.) was able to exert its anti-nociceptive and anti-infl ammatory activity through central and peripheral mechanism. BIRM was able to signifi cantly inhibit both acetic acid induced writhes and carrageenan-induced paw edema indicating it’s possible peripheral analgesic and anti-infl ammatory action. BIRM was also able to inhibit both neurogenic and infl ammatory pain in the formalin test indicating its action through central and peripheral nervous system. Conclusion: Our study results show that BIRM has the potential anti-infl ammatory property and is able to exert its anti-nociceptive effect through both central and peripheral mechanisms.

Evaluation of the anti-nociceptive potential of ethanolic extract of leaves of Bryophyllum pinnatum in experimental animals.

Background: The plant Bryophyllum pinnatum is traditionally used for the treatment of pain and inflammation. The present study was carried out to evaluate the antinociceptive effect of the ethanolic extract of the leaves of B. pinnatum (EEBP) using a hot plate method and acetic acid induced writhing test in mice. Methods: In the hot plate analgesiometer method, the time between the placement on the hot plate and the occurrence of licking of the paws, shaking or jumping off from the plate was recorded as response latency. Total numbers of stretching episodes for 30 mins immediately after acetic acid injection in all the groups were recorded in acetic acid induced writhing method. Pentazocine (10 mg/kg intraperitoneal) and aspirin (500 mg/kg) were used as the standard drugs in the hot plate and acetic acid induced writhing method, respectively. Extract was used in 200, 300 and 400 mg/ kg doses. Results: At all the three doses the EEBP showed signifi cant (p<0.01) anti-nociceptive activity in experimental models of Eddy’s hot plate analgesiometer and acetic acid induced writhing method in mice. Conclusion: The observed pharmacological activities provide the scientifi c basis to support traditional claims, as well as exploring some new and promising leads in the management of pain.

Evaluation of analgesic activity of Emblica officinalis in albino rats.

Background: Amla is one of the most often used herbs in indigenous medicine, whose all parts including fruit, seed, leaves, root, bark, and fl owers are used in various Ayurvedic/Unani medicines. However, studies to establish analgesic potential of amla were limited, so the purpose of the present study was to evaluate analgesic activity of amla, if it possesses any. Methods: Albino rats were divided randomly in three groups of six rats each. Group 1 (control) received distilled water orally, Group 2 (test) received Emblica offi cinalis extract in dose of 600 mg/kg orally and Group 3 (standard) received Pentazocine in dose 10 mg/kg intraperitoneally. Results: Emblica offi cinalis extract did not produced statistically signifi cant (p>0.05) analgesia when compared with the control group in hot plate latency, but produced a statistically signifi cant reduction in 6% NaCl induced abdominal writhing (p<0.05). Conclusions: Since the plant extract signifi cantly reduced the number of writhes in abdominal writhing model, but do not increase hot plate latency, the commercially available crude extract of Emblica offi cinalis exhibit analgesic activity involving peripheral mechanisms.

Effect of Gmelina arborea Roxb in experimentally induced infl ammation and nociception.

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

Anti-nociceptive and antimicrobial evaluation of mannich bases of 1H-Indoles.

A series of several novel mannich bases of indoles (1A-L) have been synthesized from indole by reacting with respective aldehyde and the various compounds containing secondary amine. The synthesized compounds were characterized by IR and 1HNMR spectral analysis. All the synthesized compounds were evaluated for their anti-nociceptive activity in mice by Eddy’s hot plate method. The reaction time was compared with standard drug pentazocine. In vitro antimicrobial activity of the synthesized compounds were screened against the Gram positive microorganisms such as Staphylococcus aureus, Streptococcus pyogenes, Gram negative microorganisms such as Escherchia coli, Klebsiella aerogenes and fungus Candida albicans by cup plate method. The zone of inhibition of the synthesized compounds was compared with the standard drug amikacin and ketoconazole respectively. All the synthesized compounds exhibited significant anti-nociceptive activity and showed moderate antimicrobial activity.

Anti-inflammatory and anti-nociceptive effects of Zeyheria montana (Bignoniaceae) ethanol extract

In this work, the analgesic and anti-inflammatory activities of Zeyheria montana Mart. ethanol leaf extract were investigated at doses of 75, 150 and 300 mg/kg body weight. In the analgesic assay, against a chemical stimulus in mice, acetic acid-induced writhes were significantly inhibited by the extract at doses of 75 mg/kg (67.27 percent), 150 mg/kg (49.38 percent) and 300 mg/kg (82.87 percent). Also, a vigorous decrease in hyperalgesia was observed when measured after 2 h and 6 h of lipopolysaccharide stimulation of rats for all doses of extract tested. Z. montana extract, at doses of 75 and 300 mg/kg, caused very slight central analgesia in rats submitted to thermal stimulus, particularly noticeable at 30 min following treatment. The anti-inflammatory activity of Z. montana extract on carrageenan-induced oedema in rats was evaluated. The oedema development, measured at 180 min following carrageenan intraplantar injection, was significantly reduced by all tested doses: 75 mg/kg (33.30 percent), 150 mg/kg (45.80 percent) and 300 mg/kg (75.00 percent). The LD50 value was greater than 2000 mg/kg. These results demonstrated that the ethanol extract from Z. montana leaf possesses anti-nociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.