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This study investigated the anti-inflammatory properties of Ajuga integrifolia , an herbal preparation. Qualitative and quantitative phytochemical analyses were conducted to identify active compounds in the preparation. The researchers also assessed its ability to inhibit the production of pro-inflammatory enzymes, cyclooxygenases (COX-1, COX-2), and lipoxygenase (5-LOX) in vitro. The extracts demonstrated dose-dependent inhibition of these enzymes, with some extracts showing IC 50 values comparable to standard anti-inflammatory drugs. The ethanol extract exhibited significant inhibition of 5-LOX (52.99 μg/mL), compared to the standard drug zileuton (32.41 μg/mL), while the inhibition of COX-1 (66.00 μg/mL) and COX-2 (71.62 μg/mL) was comparable to the standard drug indomethacin (40.57 and 54.39 μg/mL, respectively). These findings suggest that A. integrifolia has the potential to be used as a herbal remedy for treating inflammatory conditions. By inhibiting pro-inflammatory enzymes, the extracts may effectively reduce inflammation and promote tissue healing or repair. The inhibition potential of extract of this plant can be taken as a good candidate of anti-inflammatory agent., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Sisay Awoke Endalew and Belete Tesfaw Abebaw.)

The genus Ajuga is widely distributed in temperate to subtropical regions, and four species are currently recognized in Korea (A. decumbens, A. multiflora, A. nipponensis, and A. spectabilis), but epidermal anatomical differences across these species have never been described. A comparative study of the leaf micromorphological characteristics of Korean Ajuga species was performed using light microscopy (LM) and scanning electron microscopy (SEM) to elucidate their taxonomic usefulness and to assess leaf micromorphological diversity. Considerable diversity in epidermal and stomatal anatomy was observed across Korean Ajuga species. Species had both hypostomatic or amphistomatic leaves, with anomocytic, anisocytic, diactyic, or actinocytic stomatal complexes. Guard cell length across species ranged from 17.66 ± 0.57 μm to 32.50 ± 2.38 μm and correlated with genome size. Abnormal stomata were frequently observed in three species (A. decumbens, A. multiflora, and A. nipponensis) but not in A. spectabilis. Three types of glandular trichomes were found: peltate in all species, short-stalked in all species, and long-stalked glandular trichomes in A. multiflora. Among the investigated leaf micromophological characters, trichome type, epidermal cell shape, and stomatal morphology were all taxonomically informative traits at a species level. RESEARCH HIGHLIGHTS: A comprehensive micromorphological description of the leaf surface is provided for Korean Ajuga species using scanning electron microscopic (SEM) and light microscopic (LM) analyses. The diverse range of stomatal development and the occurrence of polymorphic stomatal types are documented for the first time in Korean Ajuga species. The great diversity in stomatal and trichome morphology in Korean Ajuga species are taxonomically useful traits for species identification., (© 2023 Wiley Periodicals LLC.)

Ajuga multiflora Bunge is a perennial ornamental herb and has been used for the treatment of fever in Korean folk medicine. In the course of searching for protective agents associated with the potential of A. multiflora against dexamethsone (DEX)-induced muscle atrophy, a new phytoecdysteroid, 29-hydroxyprecyasterone ( 1 ), together with four known compounds ( 2 - 5 ), were isolated from A. multiflora . The structures of the compounds were determined by spectroscopic analyses, including 1D-, 2D-NMR and HR-MS interpretation. To elucidate the effects of obtained compounds on DEX-induced muscle atrophy, the myotubes diameter, myosin heavy chain (MyHC) positive area, and fusion index were evaluated by immunofluorescence staining. Overall, each compound treatment effectively prevented the atrophic myotubes through an increase of MyHC-positive myotubes and the number of nuclei. Particularly, the measurement of myotube diameter showed that compounds 1 and 5 treatment significantly alleviated the myotube thickness.

Iron oxide nanoparticles (NPs) have attracted substantial interest due to their superparamagnetic features, biocompatibility, and nontoxicity. The latest progress in the biological production of Fe 3 O 4 NPs by green methods has improved their quality and biological applications significantly. In this study, the fabrication of iron oxide NPs from Spirogyra hyalina and Ajuga bracteosa was conducted via an easy, environmentally friendly, and cost-effective process. The fabricated Fe 3 O 4 NPs were characterized using various analytical methods to study their unique properties. UV-Vis absorption peaks were observed in algal and plant-based Fe 3 O 4 NPs at 289 nm and 306 nm, respectively. Fourier transform infrared (FTIR) spectroscopy analyzed diverse bioactive phytochemicals present in algal and plant extracts that functioned as stabilizing and capping agents in the fabrication of algal and plant-based Fe 3 O 4 NPs. X-ray diffraction of NPs revealed the crystalline nature of both biofabricated Fe 3 O 4 NPs and their small size. Scanning electron microscopy (SEM) revealed that algae and plant-based Fe 3 O 4 NPs are spherical and rod-shaped, averaging 52 nm and 75 nm in size. Energy dispersive X-ray spectroscopy showed that the green-synthesized Fe 3 O 4 NPs require a high mass percentage of iron and oxygen to ensure their synthesis. The fabricated plant-based Fe 3 O 4 NPs exhibited stronger antioxidant properties than algal-based Fe 3 O 4 NPs. The algal-based NPs showed efficient antibacterial potential against E. coli , while the plant-based Fe 3 O 4 NPs displayed a higher zone of inhibition against S. aureus . Moreover, plant-based Fe 3 O 4 NPs exhibited superior scavenging and antibacterial potential compared to the algal-based Fe 3 O 4 NPs. This might be due to the greater number of phytochemicals in plants that surround the NPs during their green fabrication. Hence, the capping of bioactive agents over iron oxide NPs improves antibacterial applications.

The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds 1 - 3 , were isolated from Ajuga ovalifolia var. calantha . Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound 2 selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound 2 targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound 2 passed the majority of the parameters of common drug discovery rules. Compound 2 restrained A549 proliferation (IC 50 = 8.68 ± 0.96 μM), invasion and caused A549 cell apoptosis by inhibiting the SHP2-ERK/AKT signaling pathway. Finally, compound 2 (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment.

Two new 3,4-epoxy group-containing abietane diterpenoids ( 1 and 2 ), together with five known diterpenoids ( 3 - 7 ), were isolated from Ajuga decumbens . Their structures were elucidated by spectroscopic data analysis, NMR calculations, and X-ray diffraction experiments. The structures of two known abietane diterpenoids were revised based on NMR calculations and X-ray diffraction data. Notably, compound 4 specifically inhibited RSL3-induced ferroptosis with an EC 50 of 56 nM by antioxidation. Moreover, 4 significantly decreased RSL3-induced lipid and cytosolic ROS accumulation and ferroptosis marker gene PTGS2 mRNA expression. This work reports the most potent natural inhibitor against ferroptosis found so far.

Introduction: Panama's HIV epidemic is far from under control. One of the populations with the fastest-growing epidemic among the Indigenous peoples of the Comarca Ngäbe-Buglé (CNB). The CNB is an administratively autonomous Indigenous region in Western Panama that is home to over 200,000 individuals of Ngäbe and Buglé ethnicities. This population is unique and, in several ways, represents the early stages of the AIDS epidemics in high-income countries. The CNB is the most impoverished region in Panama and is relatively isolated from outside influences, with limited roads, electricity, and an internet connection, including medical assistance. Around 1.5% of all rapid HIV tests are positive, compared to a national prevalence of 0.9%; in CNB, diagnosis tends to be late. In CNB, 56.3% of individuals had an initial CD4 count of <350 cells/mm3. Antiretroviral treatment (ART) dropout in this region is five times higher than the national average; there is high early mortality due to opportunistic infections. Using the Social-Ecological Theory for Health as a framework, this study aims to describe the facilitators and barriers associated with ART adherence and retention in HIV care among people living with HIV (PLHIV) in the CNB. A better understanding of factors that obstruct adherence could lead to more effective HIV care and prevention in CNB., Methods: We conducted 21 semi-structured interviews with PLHIV who reside across all three regions of the CNB and have attended an antiretroviral (ART) clinic at least once. Deductive thematic analysis was used to uncover themes related ART adherence and retention in HIV care at the individual, social and structural levels., Discussion: This unique, isolated population of rural Indigenous peoples has high infection rates, late diagnosis, poor ART adherence, and high AIDS-related death rates. The CNB is an important region to examen ART adherence and retention in care. We determined that psychological health, social support, and discrimination acted as individual-level facilitators and barriers to adherence and retention. Notably, structural barriers included difficult access to ART care due to travel costs, ART shortages, and uncooperative Western/Traditional medical systems. Recommended interventions used in other Low- and Middle-Income settings include increasing peer and family-level support and community knowledge and understanding of HIV infection. Additionally, our study suggests structural interventions, including decreasing the cost and distance of traveling to the ART clinic, by decentralizing services, decreasing food scarcity, and increasing collaboration between Western and Traditional providers., Competing Interests: The authors have declared that no competing interests exist.

Background: Ajuga bracteosa is a traditional herb used against various diseases., Objectives: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu)., Methods: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration., Results: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepatoprotective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity., Conclusion: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepatoprotective phytoconstituents, which could be used in the prevention of diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Lamiaceae plant Ajuga forrestii Diels is a traditional Chinese herbal medicine with abundant glandular trichomes (GTs), but their chemistry and biological functions remain uninvestigated. Here, a panel of six highly functionalized neo-clerodane diterpenoids was localized to the peltate GTs of A. forrestii using laser microdissection coupled with HPLC analysis, indicating that the GTs of A. forrestii are an excellent material for the elucidation of the yet unclear biosynthetic pathway of natural neo-clerodane diterpenoids. In addition, four undescribed neo-clerodane diterpenoids with an acyclic C-9 side chain including two pairs of 1:1 mixture of inseparable diastereomers, ajuforrestins D-G, were isolated from the fresh leaves of A. forrestii together with six known compounds. The structures of the undescribed compounds were elucidated by spectroscopic (including 1D and 2D NMR and HR-ESI-MS) analyses. Biological assays indicated that the major GT compound ajugacumbin B and undescribed ajuforrestins D/E showed antifeedant activity against Helicoverpa armigera, suggesting that neo-clerodanes in A. forrestii should be involved in plant defence against insects. Moreover, the abietane diterpenoid ajuforrestin B exhibited significant anti-inflammatory activity on the secretion of interleukin-2 (IL-2) and cytotoxicity against three cancer cell lines, NCI-H1975, HepG2 and MCF-7, suggesting that ajuforrestin B could positively contribute to the therapeutic effects of this traditional Chinese medicine., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Owing to its traditional applications, the current study focuses on Ajuga parviflora (A. parviflora) leaves extract for phytochemical and pharmacological analysis. The principle constituents were identified through gas chromatography (GC), and gas chromatography/mass spectroscopy (GC/MS), these includes phthalic acid, squalene, α-tocopherol, vitamin E, phytol, 2-methylenecholestan-3-ol, stigmasterol, cholest-22-ene-21-ol and 3,5-dehydro-6-methoxy. Hepatoprotective effect of A. parviflora was evaluated through isoniazid and rifampicin (INH and RFP) induced hepatotoxicity in rat. Animals in group A were treated with INH and RFP 50 mg/kg. Animals in group B, C, and D were pre-treated with A. parviflora extract at 100, 200 and 300 mg/kg dose prior drug administration. A. parviflora extract at 200 and 300 mg/kg in group C and D significantly reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin (p<0.001) as compare to group B (100mg/kg). Total protein (TP) was also significantly (p<0.01) reduced in group C and D at dose of 200 and 300 mg/kg, respectively. The extract pre-treated animals with (A. parviflora, 200, and 300 mg/kg) showed that the epithelium of the central portal vein is intact with replete glucagon. The pre-treatment with A. parviflora protected the liver from INH and RFP induced hepatotoxicity. The results of pre-treated animals with A. parviflora 200, and 300 mg/kg dose prettily revert the severely disturb parameters like, cytolysis, lymphocytic infiltration, and lymphoid aggregate in portal vein and hydropic degeneration. The decrease peroxisome proliferator-receptor activator-δ (PPAR-δ) gene expression by INH, and RFP was significantly up regulated by A. parviflora extract in pre-treated animals at 200 and 300 mg/kg dose. These findings provide baseline pharmacological uses of A. parviflora in liver disorders. Further investigations are required for identification and isolation of biologically active components responsible for pharmacological activity.

Herkogamy is an effective way to reduce sexual interference. However, the separation of stigma and anther potentially leads to a conflict because the pollen may be placed in a location on the pollinator different from the point of stigma contact, which can reduce pollination accuracy. Floral mechanisms aiming to resolve this conflict have seldom been explored. The floral biology of protandrous Ajuga decumbens was studied to uncover how the herkogamy dilemma can be resolved. Flower anthesis was divided into male, middle, female and wilting phases. The positions of stigma and stamen were dissimilar in different flower development stages. We measured the distance of the stamen and stigma to the lower corolla lip at different floral phases, which was the pollinators' approaching way. The pollen viability, stigma receptivity, pollen removal and pollen deposition on stigma were investigated at different phases. During the male phase, the dehisced anthers were lower than the stigma, located at the pollinators' approaching way, and dispersed most pollen with high viability. As the flower developed, the anthers moved upwards, making way for pollen deposition during the female phase. Meanwhile, the stigma becomes receptive by moving into the way and consequently was deposited with sufficient pollen. The position exchange of the stamen and stigma created a dynamic herkogamy at the floral phase with different sexual functions. This floral mechanism effectively avoided sexual interference and maintained pollination accuracy. In Ajuga , the movement herkogamy might be of adaptive significance in response to the changes in the pollination environment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Ajuga bracteosa an important medicinal herb, is getting endangered worldwide due to destructive harvesting by pharmaceutical industries in its different habitats. It is in dire need for protection and demands conservation and sustainable utilization. In the present study, effects of α-naphthalene acetic acid (NAA) under different spectral lights were estimated on the growth, secondary metabolism and biosynthesis of phenolic acids in adventitious roots (AR) cultures of A. bracteosa. Among the different spectral lights, highest AR induction frequency (88%) and formation of biomass (72 g/L FW and 22 g/L DW) were recorded in explants incubated in the presence of 1.5 mg/L NAA under yellow light. Maximum production of poly phenols (TPC;44.2 mg) and flavonoids (TFC;2.51 mg) were recorded in the AR cultures grown in the presence of blue light. Further, highest total protein content of (401.6 μg) was detected in the AR in response to normal white light. Blue spectral light induced maximum superoxide dismutase (SOD; 2.5 nM) and peroxidase activity (POD;0.85 nM) respectively, in AR cultures. Compared with other monochromatic lights, red light significantly enhanced the antioxidant potential of the AR cultures. Analysis through High performance liquid chromatography (HPLC-DAD) revealed significant variations in the levels of important phenolic acids such as gallic acid, catechin, rutin, caffeic acid, myricetin and apigenin in the AR samples treated with the lights of different spectra., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Context: Ajuga ovalifolia Bur. et Franch. var. calantha (Diels) C. Y. Wu et C. Chen (Labiatae), a traditional Chinese medicine, has been used to treat several inflammatory diseases., Objective: To assess the anti-inflammatory activity of ajudecumin A isolated from Ajuga ovalifolia var. calantha, and its possible mechanisms., Materials and Methods: Lipopolysaccharide (LPS, 0.5 μg/mL)-stimulated RAW264.7 macrophages were used to assess the anti-inflammatory activity of ajudecumin A (1-40 μM) in vitro. Nitric oxide levels were evaluated by Griess reagent. The mRNA levels of iNOS, COX-2, TNF-α, IL-1β and IL-6 were determined using qRT-PCR. Phosphorylation of ERK, JNK, p38 MAPK and IκBα were detected by western Blot. To further assess the anti-inflammatory of ajudecumin A in vivo, mice were oral treated with ajudecumin A (10 mg/kg) or dexamethasone (0.25 mg/kg, positive control) for 5 days before administration of carrageenan or xylene. Paw and ear edema were then measured, respectively., Results: Ajudecumin A (10-40 μM) decreased LPS-induced nitric oxide production with an IC 50 value of 16.19 μM. Ajudecumin A (20 and 40 μM) also attenuated cell spreading and formation of pseudopodia-like structures, and decreased the mRNA levels of iNOS (55.23-67.04%, p < 0.001), COX-2 (57.58-70.25%, p < 0.001), TNF-α (53.75-58.94%, p < 0.01-0.001), IL-1β (79.41-87.85%, p < 0.001) and IL-6 (54.26-80.52%, p < 0.01-0.001) in LPS-activated RAW264.7 cells. Furthermore, ajudecumin A suppressed LPS-induced phosphorylation of ERK, p38 MAPK, and IκBα, as well as IκBα degradation (p < 0.05-0.001). Finally, ajudecumin A (10 mg/kg) attenuated carrageenan- and xylene-induced inflammation in mice by about 28 and 24%, respectively., Discussion and Conclusions: Ajudecumin A exhibited a potent anti-inflammatory activity in vitro and in vivo through inhibition on NF-κB and ERK/p38 MAPK pathways, suggesting that ajudecumin A may be potentially developed as a lead compound in anti-inflammatory drug discovery.

Objective and Design: To characterize the impact of inflammatory process and oxidative stress in the degree of benign prostatic hyperplasia (BPH), a common condition in which chronic inflammation plays a crucial role, we investigated the effect of different plant extract preparations in an in vivo model of BPH as new therapeutic target., Material: BPH was made in rats with daily administration of testosterone propionate (3 mg/kg) for 14 days., Treatment: Rats were randomized into different groups to receive oral administration of plant extract preparations: Serenoa repens with selenium (SeR 28.5 mg/kg associated with Se 0.005 mg/kg), Teoside (2 mg/kg), and Puryprost (14 mg/kg containing Teoside 50% 2 mg/kg and Epilobium 12 mg/kg)., Methods: After 14 days, rats were killed and histological changes, prostate weight and apoptotic pathways were assayed., Results: The results obtained demonstrated that the association of treatments reduced prostate weight and hyperplasia, while treatment with Puryprost demonstrated a greater trend of protection compared to the other treatments., Conclusion: Thus, our results indicate that plant extract could be considered as new useful therapy in the treatment of BPH with particular attention on Puryprost that represents a rational approach to reduce BPH through modulation of inflammatory process and anti-oxidant process.

Light is an important physical factor necessary for the growth, morphogenesis and production of bioactive compounds in plants. In this study, effects of different photoperiod regimes and hormonal elicitors were investigated on the accumulation of biomass, antioxidant potential and biosynthesis of secondary volatiles in the cell cultures of Ajuga bracteosa. Maximum accumulation of biomass (13.2 g/L) was recorded in cell cultures established at 1.0 mg/L benzylaminopurine (BA) in exposure to continuous dark. Biochemical assays showed that in the presence of 0.5 methyl jasmonate (Me-J), cell cultures grown under continuous dark had the higher activities of superoxide dismutase (SOD: 4.5 U/mg), peroxidase (POD: 3.1 U/mg), total phenolic content (TPC: 8.1 mg GAE/g of DW) and total flavonoid content (TFC: 5.2 mg QE/g of DW) respectively. Nonetheless, the free radical scavenging activity (FRSA) was found correlated with the phenyl ammonia lyase (PAL) activity in the dark grown cell cultures. Analysis through gas chromatography-mass spectrometry (GC-MS) showed, biosynthesis of 29 compounds in the in vitro raised cell cultures. The major identified compounds consisted of monoterpene hydrocarbons such as β-pinene (2.1-9.5%), β-ocimene (1.4-8.3%), 1-terpinene-4-ol (5.8-9.6%), caryophyllene (1.3-6.2%), β-farnesene (0.82-7.8), oxygenated monoterpenes including myrtenal (2.2-8.4%), citronellyl acetate (2.1-7.3%) and sesquiterpenes such as caryophyllene oxide (1.5-5.5) and β-elemene (2.2-8.8%). This protocol has the potential for commercial production of important secondary volatiles., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present study investigated the protective effect of phytoecdysteroids extracted from the Ajuga iva plant on body weight changes, blood glucose, insulin total protein, blood urea nitrogen (BUN), creatinine, triglycerides (TG), cholesterol, lipid peroxidation, antioxidant enzymes, pancreatic histopathology and hexokinase-I expression in the alloxan-induced diabetic rats. Experimental diabetes was induced following 15day intraperitoneal administration of alloxan. The rats were divided into four groups. Group I served as a sham group, and group II served as the diabetic control. Group III served as a treatment for phytoecdysteroids (10mg/kg), and group IV served as a treatment for phytoecdysteroids (20mg/kg). Phytoecdysteroids restored body weight loss to its antihyperglycemic effect. Blood glucose was reduced 19.2 and 52.9% in group III and IV respectively. Blood insulin (54.9 and 105.88%) and total protein (25 and 72.2%) was increased in group III and IV respectively. BUN, creatinine, TG, cholesterol and lipid peroxidation was significantly reduced following treatment. Catalase, superoxide dismutase (SOD), and glutathione peroxidase activity were significantly increased following treatment. Islet β-cells are lost in alloxan-induced diabetic rats. Regeneration of islets and reduced atrophy of acinar cells were noted. The number of insulin-secreting cells was tremendously reduced in alloxan-induced diabetic rats. Insulin-secreting cells were increased 48 and 61% in group III and IV respectively. Hexokinase-I mRNA (28.3 & 93.5%) and protein (27.9 and 55.3%) expression were significantly increased following treatment. Taking all these data together, it is suggested that the phytoecdysteroid could be a potential therapeutic agent against experimental diabetes., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Ajuga bracteosa is a medicinally important plant globally used in the folk medicine against many serious ailments. In the present study, effects of two significant elicitors, methyl jasmonate (Me-J) and phenyl acetic acid (PAA) were studied on growth parameters, secondary metabolites production, and antioxidant potential in adventitious root suspension cultures of A. bracteosa . The results showed a substantial increase in biomass accumulation, exhibiting longer log phases of cultures growth in response to elicitor treatments, in comparison to control. Maximum dry biomass formation (8.88 DW g/L) was recorded on 32nd day in log phase of culture when  0.6 mg/L Me-J was applied; however, PAA at 1.2 mg/L produced maximum biomass (8.24 DW g/L) on day 40 of culture.  Furthermore, we observed the elicitors-induced enhancement in phenolic content (total phenolic content), flavonoid content (total flavonoid content) and antioxidant activity (free radical scavenging activity) in root suspension cultures of A. bracteosa. Application of 0.6 mg/L and 1.2 mg/L of Me-J, root cultures accumulated higher TPC levels (3.6 mg GAE/g DW) and (3.7 mg GAE/g DW) in the log phase and stationary phase, respectively, while 2.5 mg/L Me-J produced lower levels (1.4 mg GAE/g DW) in stationary phase of growth stages. Moreover, TFC and FRSA values were found in correspondence to TPC values in the respective growth phases at the similar elicitor treatment. Thus, a feasible protocol for establishment of adventitious roots in A. bracteosa was developed and enhancement in biomass and metabolite content in adventitious root was promoted through elicitation.

Background: The genus Ajuga is used for the treatment of joint pain, gout, and jaundice in traditional Iranian medicine (TIM). Ajuga chamaecistus ssp. tomentella is an exclusive subspecies of Ajuga chamaecistus in the flora of Iran. The aim of this study was to evaluate antinociceptive properties of some extracts from aerial parts of A. chamaecistus ssp. tomentella., Methods: Antinociceptive activities of total water and 80% methanol extracts, hexane, diethyl ether and n-butanolic partition fractions of the methanolic extract were analyzed using the formalin test in mice. Indomethacin (10 mg/kg) and normal saline were employed as positive and negative controls, respectively., Results: Oral administration of all extracts (200, 400 and 600 mg/kg) 30 min before formalin injection had no effect against the acute phase (0-5 min after formalin injection) of the formalin-induced licking time, but hexane fraction (200 mg/kg) caused a significant effect (p < 0.001) on the chronic phase (15-60 min after formalin injection). Total water and diethyl ether extracts at a dose of 400 mg/kg showed a very significant analgesic activity on the chronic phase (p < 0.001 and p < 0.01, respectively)., Conclusions: The results of this study suggest that the extracts of A. chamaecistus ssp. tomentella have an analgesic property that supports traditional use of Ajuga genus for joint pain and other inflammatory diseases.

Four neo-clerodane diterpenoids, neoajugapyrin A, scutegalerins A and B and scutecolumnin C have been isolated from the acetone extract of the aerial parts of Scutellaria galericulata. Neoajugapyrin A and scutecolumnin C are reported in this species for the first time, whereas scutegalerins A and B are new compounds. NMR data of neoajugapyrin A ar e discussed i n detail t o support t he proposed revised structure of ajugapyrin A.

Methanolic extract of medicinal herb Ajuga parviflora Benth. was evaluated for phytochemical screening (the plant extract showed the presence of aromatic compounds, carbohydrates, glycosides, tannins, alkaloids, polyphenols, quinines and dions, aminophenols, steroids/sterols, flavonoids and terpenoids), antimicrobial activities against various strains of bacteria and fungi by using disc diffusion method and insecticidal activities against red flour beetle (Tribolium castaneum), wheat weevil (Sitophilis granaries) and their larvae. The crude extract showed anti-bacterial activity against all strains with a maximum zone of inhibition of 12mm diameter against Citrobacter and Pseudomonas aurogenosa. Standard drugs Ampicillin, Gentamicin and Amoxicillin were used in parallel. The crude extract did not show antifungal activity against the tested strains of fungi even at high doses. The crude methanolic extract was also used for insecticidal activity against the two types of insects and their larva. The extract showed no significant mortality in the tested strains. For brine shrimp lethality bioassay different concentrations 10, 100 and 1000ug/ml of the medicinal herb A. parviflora methanolic extract were used. After 24 hrs the percent mortality and LD50 value was calculated through probit analysis. The LD50 value of extract was 321.42μg/mL while that of standard drug cyclophosphamide was 16.09ug/ml.

8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

Ethnopharmacological Relevance: Ajuga decumbens Thunb is a medicinal plant native to China popularly used to treat chronic pelvic inflammation and hysteromyoma. Its main bioactive components are iridoid glycosides, such as 8-O-acetylharpagide and harpagide that had presented antibacterial, anti-inflammatory, and antiviral activities., Aim of the Study: To establish a sensitive LC-MS/MS method and compare the pharmacokinetics of 8-O-acetylharpagide and harpagide in rats after oral administration of their pure forms and from compounds obtained from Ajuga decumbens extract., Materials and Methods: Rats received orally 15 mg/kg (equivalent of 6 mg/kg 8-O-acetylharpagide and 1.5mg/kg harpagide), 30 mg/kg and 60 mg/kg of Ajuga decumbens Thunb extract and were compared to animals that received 12 mg/kg of 8-O-acetylharpagide or 3mg/kg of harpagide p.o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartmental analysis., Results: Results showed that the iridoid glycosides were quickly absorbed by oral route and showed a dose-dependence profile. Pharmacokinetic parameters of both glycosides were essentially the same except Tmax when dosed as the extract or pure forms., Conclusion: 8-O-acetylharpagide was metabolized to harpagide, which affected the pharmacokinetic profiles of harpagide when dosed as the extract. This pharmacokinetic study seems to be useful for a further clinical study of Ajuga decumbens Thunb extract., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to determine the effects of Ajuga iva aqueous extract on lecithin : cholesterol acyltransferase (LCAT) activity and amount and composition of high-density lipoprotein (HDL)(2) and (HDL)(3), in streptozotocin (STZ)-induced diabetic rats., Methods: Diabetes was induced in male Wistar rats by intraperitoneal injection of STZ (60 mg/kg body weight). Diabetic rats (n = 12) were divided into two groups. The diabetic control group (D) received a 20% casein diet and the diabetic treated group received the same diet supplemented with A. iva aqueous extract (0.5 g/100 g diet) (DAi), for 4 weeks., Key Findings: Total cholesterol and HDL(3) -C were respectively decreased by 32% and 55% in the DAi group compared with the D group, whereas HDL(2)-C was increased by 30%. The amounts of HDL(2) and HDL(3), which were the sum of apolipoproteins, unesterified cholesterol (UC), cholesteryl esters (CEs), triacylglycerols (TGs) and phospholipids (PLs), showed no significant difference. A. iva treatment increased LCAT by 33% and its cofactor-activator, apolipoprotein A-I, by 58%. HDL(3)-PL (enzyme substrate) and HDL(3)-UC (acyl group acceptor) were respectively decreased by 70% and 57%, whereas HDL(2)-CE (product of LCAT reaction) was enhanced by 30%., Conclusions: In STZ-induced diabetic rats, A. iva improves reverse cholesterol transport by enhancing LCAT activity, leading to anti-atherogenic effects., (© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.)

We investigated the in vivo activity of crude water extracts of Ajuga remota Benth (Labiatae) against Plasmodium berghei in mice using plants harvested from two areas in Kenya where the plant is commonly used to treat malaria. The extract was tested using a 4-day test at a dose of 30 mg/kg/day (equivalent to 0.2 ml solution per mouse). Wet leaf extract was the most effective with 90.4% suppression of parasitemia. Extract from air-dried and powdered flowers were the least effective with 17.2% suppression of parasitemia.

Objective: To investigate the anticancer and anti-metastatic effect of Ajuga decumbens extraction (HBG) on breast cancer and to clarify the effect of HBG on MMPs and TIMPs., Method: The antitumor and antimetastic effect of HBG was determined using orthotopic 4T1 breast cancer mouse model. Western blot analysis was employed to detect the expression of associated proteins in breast cancer metastasis., Result: Administration with 50-200 mg x kg(-1) doses of HBG significantly reduced the tumor weight, tumor volume and numbers of lung tumor nodules in a dose-dependent manner. Tumor metastasis correlated proteins were altered following HBG treatment, MMP-2 and MMP-9 were down-regulated while TIMP-1 and TIMP-2 were up-regulated., Conclusion: HBG showed anticancer and antimetastatic effect towards breast cancer through regulating the expression of MMPs and TIMPs. These data sustain our contention that HBG might be used as a potential therapeutic agent.

Ethnopharmacological Relevance: The entire plant of Ajuga bracteosa Wall has been used to treat various inflammatory disorders, including hepatitis, in Taiwan., Aim: This study evaluated the hepatoprotective ability of Ajuga bracteosa extract (ABE)., Materials and Methods: We investigated the inhibitory action of a chloroform fraction of ABE (ABCE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and Kupffer cells. Hepatic fibrosis was induced in mice through the administration of CCl(4) twice a week for 8 weeks. Mice in three CCl(4) groups were treated daily with water and ABE throughout the duration of the experiment., Results: In LPS-stimulated RAW264.7 cells and Kupffer cells, ABCE inhibited the production of NO and/or TNF-α and also blocked the LPS-induced expression of NO synthase. ABCE inhibited the activation of NF-κB induced by LPS, associated with the abrogation of IκBα degradation, with a subsequent decrease in nuclear p65 and p50 protein levels. The phosphorylation of MAPKs in LPS-stimulated RAW264.7 cells was also suppressed using ABCE. In the in vivo study, ABE protected the liver from injury by reducing the activity of plasma aminotransferase, and by improving the histological architecture of the liver. RT-PCR analysis showed that ABE inhibited the hepatic mRNA expression of LPS binding protein, CD14, TNF-α, collagen(α1)(I), and α-smooth actin., Conclusion: These results indicate that ABE alleviated CCl(4)-induced liver fibrosis, and that this protection is probably due to the suppression of macrophage activation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The aim of the current study is to investigate the therapeutic and preventive effects of 1alpha, 25dihydroxyvitaminD3 (1,25 (OH)2 D3) and Afuga iva (AI) extract on diabetes toxicity in rats testes. Thus diabetic rats were treated with 1alpha, 25dihydroxyvitaminD3 or Ajuga iva extract as both therapeutic and preventive treatments on diabetes toxicity in rats testes. Our results showed that diabetes induced a decrease in testosterone and 17beta-estradiol levels in testes and plasma. Besides, a fall in testicular antioxidant capacity appeared by a decrease in both antioxidant (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities) and nonenzymatic antioxidant (copper (Cu), magnesium (Mg) and iron (Fe) levels). All theses changes enhanced testicular toxicity (increase in testicular aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH) activities and the lipid peroxidation and triglyceride (TG) levels). In addition, a decrease in testicular total cholesterol (TCh) level was observed in diabetic rats testes. All the changes lead to a decrease in the total number and mobility of epididymal spermatozoa. The administration of 1alpha,25dihydroxyvitaminD3 and Ajuga iva extract three weeks before and after diabetes induction interfered and prevented diabetes toxicity in the reproductive system. 1,25 (OH)2 D3 and Ajuga iva extract blunted all changes observed in diabetic rats. To sum up, the data suggested that 1,25 (OH)2 D3 and Ajuga iva extract have a protective effect on alloxan-induced damage in reproductive system by enhancing the testosterone and 17beta-estradiol levels, consequently protecting from oxidative stress, cellular toxicity and maintaining the number and motility of spermatozoids.

The aim of the study was to investigate the effect of aqueous extract of Ajuga iva (Ai) on serum and tissues lipid peroxidation as well as antioxidant enzymes activities in red blood cells (RBC) and tissues, in high hypercholesterolemic rats (HC). Male Wistar rats (n=12) were fed on 1% cholesterol-enriched diet for 15d. After this adaptation phase, hypercholesterolemic rats (total cholesterol=6.5+/-0.6mol/l) were divided into two groups fed the same diet and treated or not with Ai for 15d. Thiobarbituric acid reactive substances (TBARS) concentrations in serum, LDL-HDL(1), HDL(2) and HDL(3) were respectively, 5-, 7.8-, 2.3- and 5-fold lower in Ai treated than untreated hypercholesterolemic groups. TBARS concentrations were 1.4-fold lower in heart and 2.8-fold higher in kidney in Ai-HC treated than untreated HC group. Superoxide dismutase activity was respectively, 1.2- and 1.4-fold higher in RBC and muscle in Ai treated than untreated group. In RBC, Ajuga iva treatment enhanced glutathione peroxidase (GSH-Px) (+9%) and glutathione reductase (GSSH-Red) (+12%) in Ai-HC treated than untreated HC group. GSSH-Red activity was 1.4- and 1.5-fold higher in adipose tissue and heart, respectively and 3.7-fold lower in kidney in Ai treated than untreated group. Liver catalase activity was 1.6-fold higher in Ai treated than untreated group. Adipose tissue and muscle total glutathione content represented in Ai treated group 35% and 36% of the value noted in untreated group. Nitric oxide values of liver, adipose tissue and heart were 3.3-, 2.5- and 3.4-fold higher in Ai-HC than HC group. Ajuga iva treatment enhanced alpha-tocopherol contents (+25%) in Ai treated than untreated group. In conclusion, Ajuga iva treatment is more effective to improve the antioxidant capacity of RBC than that of tissues. Indeed, Ai is able to reduce the oxidative stress in hypercholesterolemic rats by increasing the antioxidant enzymes activity.

The hypoglycemic and hypolipidemic effect of continuous intravenous infusion of a lyophilised aqueous extract of the whole plant Ajuga iva (L.) Schreber (Labiatae) (AI-extract) was investigated in anesthetized normal and streptozotocin (STZ)-induced diabetic rats. The AI-extract was administered to a group of rats by continuous intravenous infusion for 4 h at a dose of 4.2 microg/min/100 g body weight; another group was infused with taurine, the reference compound, at the same dose. In normal rats, AI-extract infusion had no effect on plasma glucose or triglycerides, but plasma cholesterol levels were significantly decreased (22%; P<0.05). However, taurine infusion produced significant hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects (all changes, P<0.05). In STZ-diabetic rats, AI-extract infusion reduced plasma levels of glucose by 24 % (P<0.05), cholesterol by 35% (P<0.01) and triglycerides by 13% (P<0.05). Infusion with taurine produced a greater fall in plasma glucose (72%, P<0.01), cholesterol (54%; P<0.001) and triglyceride (24%; P<0.001) levels. Our results indicate that intravenously administered AI-extract exerts hypoglycemic and hypolipidemic effects in diabetic rats by mechanism(s) which appear to be similar to that of taurine, which involve insulin sensitization or an insulin-like effect. The identity and the exact mechanism(s) of action of the active component(s) of the AI-extract are not known. Ajuga iva appears to be a useful plant in the therapy of diabetes, a condition in which hyperglycemia and dyslipidemia coexist quite often.

Aquaporins (AQPs) are proteins that facilitate the transport of water across cell membranes. AQP3 expression is related to the expressions of other epidermal proteins involved in water maintenance (ie, CD44, claudin-1, and filaggrin). The expressions of AQP3 water channels are strongly affected by age and chronic sun exposure, and a defective osmotic equilibrium could occur in the epidermis, which would account for the skin dryness observed in older people and skin areas most exposed to sunlight. We investigated active ingredients that are able to increase AQP3 levels in order to improve hydration in human skin keratinocytes. We selected an ethanolic/water (70/30 v/v) extract of Ajuga turkestanica, a plant from Central Asia, as the hydrating agent. After 17 days of treatment every 2 days with this extract (2.5 microg/mL) in vitro, AQP3 expression measured at the protein level in human reconstructed epidermis was significantly increased. Water transport through both aquaporins and aquaglyceroporins and glycerol transport through aquaglyceroporins alone are important to skin hydration. The distribution and the variability of aquaporins in human skin cells suggest that these channels may have important roles in skin physiology. AQPs appear to be key protein targets to improve the resistance and quality of the skin surface as well as to improve aging and sun exposure-induced dryness as shown by their roles in 1) hydrating the living layers of the epidermis where the keratinocyte differentiation takes place and 2) barrier formation and recovery.

Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular (CV) morbidity and mortality in diabetic patients. The plant Ajuga iva (L.) Schreiber (Labiatea) is used in the treatment of diabetes in Moroccan folk medicine. Previously, we have demonstrated potent hypoglycemic activity and relatively non-toxic nature of a lyophilized aqueous extract of the whole plant (AI-extract) in normal (normoglycemic) and streptozotocin (STZ)-diabetic rats. In this study, we examined the AI-extract for its possible lipid-lowering activity in normal and STZ-diabetic rats. Taurine (TR) and glibenclamide (GLB) were used as reference substances. As shown previously, the AI-extract (10 mg/kg; oral) reduced plasma glucose levels after acute (single) and sub-chronic (3 weeks) dosing both in normal and diabetic rats. In normal rats, single and repeated oral administration of the AI-extract, at a dose of 10 mg/kg produced a small but significant decrease in plasma CHL levels (P<0.05). A single dose of the AI-extract did not produce a significant change in plasma TG, but sub-chronic dosing (for up to 21 days) caused a significant decrease in plasma TG (P<0.05). In STZ-diabetic rats, a single dose as well as repeated (3 weeks) treatment with the AI-extract produced a significant decrease in plasma CHL (P<0.01), and triglyceride (P<0.01) levels. The AI-extract also prevented weight loss in the diabetic animals. In summary, an aqueous extract of the Ajuga iva whole plant showed hypolipidemic activity, in addition to its hypoglycemic effect in normoglycemic and diabetic rats. In view of the hypoglycemic and hypolipidemic activity, and its relatively non-toxic nature (shown previously), Ajuga iva may be a candidate for development as an anti-diabetic agent in humans. Further studies are warranted to confirm our results and fractionate the AI-extract to isolate and identify the active principle(s), and to determine the exact mechanism(s) of action.

Background: There are quite large number of traditionally used plants that are used to treat ailments associated with fever in the ethnomedical system of Ethiopia. Most of them, however, have not been subjected to scientific investigation for their efficacy and safety., Objectives: To evaluate the antipyretic effects of the aqueous and ethanol extracts of the leaves of Ajuga remota and Lippia adoenesis., Design: An experimental design in which five group of in-house bred albino mice weighing 30-35 g representing positive and negative control, and three dose levels extract treated groups, respectively was employed. The extracts, standard drugs and distilled water were administered into GIT by gavage to evaluate the antipyretic effect after inducing pyrexia in mice., Results: All extracts of both plants that were administered orally at doses of 50, 100 and 200 mg per kg showed antipyretic property. The antipyretic effects were observed to be dose dependent. In both plants, the aqueous extract was found to have more potent antipyretic effect than the ethanol extract. No mouse manifested toxic effects at any dose levels of all the extracts for the observed period of two weeks., Conclusion: The present study show that both extracts of the investigated plants have got antipyretic effects and the extracts are effective and safe at the doses tested. This supports the traditional claim or use of these plants.

A 58-year-old man ingested an herbal preparation of Ajuga nipponesis Makino, as recommended in folk medicine for the treatment of hepatoma. He developed profound gastrointestinal upset immediately, and decreasing urine output and bilateral leg edema over the following 2 days. Notable laboratory findings included elevated levels of blood urea nitrogen, creatine, bilirubin, and hepatic transaminases. Deterioration of renal function was noted during hospitalization and he died 11 days after ingesting the herbal preparation. Two other healthy individuals also consumed the same herbal preparation at the same time but developed only vomiting and diarrhea. One or more of the four major components of Ajuga nipponesis Makino may be responsible for the renal toxicity found in our patient.

The aim of the present study was to investigate the ex vivo and in vitro vascular activity of the aqueous extract of Ajuga iva (L.) Schreber (Labiatae) in normotensive Wistar rats. Chronic oral administration of the extract of Ajuga iva did not significantly affect the systolic blood pressure. In aorta isolated from Ajuga iva-treated rats, the contractile response to noradrenaline was depressed compared to the responses obtained in aorta from untreated rats but the endothelium-dependent relaxation evoked by acetylcholine was not affected. In vitro, Ajuga iva extract inhibited the contraction evoked by noradrenaline. The addition of Ajuga iva extract during the plateau phase of noradrenaline-evoked contraction produced a relaxation that was sensitive to N-nitro-L-arginine. After pre-incubation of the artery in the presence of the plant extract, vasorelaxant effect was markedly less pronounced. The endothelium-dependent relaxation induced by acetylcholine was concentration-dependently blunted in the presence of Ajuga iva extract in the bathing solution. This study indicates that the aqueous extract of Ajuga iva possesses NO-mediated and NO-independent vasorelaxing properties in vitro while only the endothelium-independent effect was observed ex vivo.

Ajuga iva (L.) Schreber (AI), is widely used in the Moroccan pharmacopoeia as a panacea (cure-all), and specifically for gastrointestinal disorders and diabetes, and as an anthelmintic. No toxicological investigations have been carried out on this plant. We have previously observed that single oral doses (2-14 g/kg) of a lyophilised aqueous extract of AI (AI-extract) in mice or daily oral administration of 10 mg/kg of AI-extract in rats for 2 weeks did not result in any adverse effects. We have now evaluated AI-extract for its behavioural and pharmaco-toxicological effects after acute and chronic administration by the oral and intraperitoneal routes in rats and mice. No toxicity was observed in mice after single oral doses of as high as 14 g/kg of the AI-extract. However, single intraperitoneal injections of the AI-extract (1500-5500 mg/kg BW) produced a dose-dependent increase in adverse effects in the general behaviour and the mortality rate; the LD50 of acute intraperitoneal dose was 3.6 g/kg. In chronic toxicological studies in rats, the AI-extract (administered orally at daily doses of 100, 300 and 600 mg/kg for 3 months), did not cause any changes in haematological and biochemical parameters, with the exception of a transient rise in platelet counts and a short-term decrease in serum glucose levels. Histopathological examination of the brain, liver and the kidneys at the end of the study (3 months) showed normal architecture suggesting no morphological disturbances.

Many people use analgesic plants to relieve pain and inflammation though most of them have not yet been proved to possess such properties. The objective of the present study was to screen the aqueous and ethanol extracts of four Ethiopian traditionally used medicinal plants for analgesic properties. Aqueous and ethanol extracts of the plant materials were screened for their analgesic properties in mice using tail-flick, hot-plate and tail-pinch tests at three dose levels. Normal saline and standard analgesics were employed as negative and positive controls, respectively. The plants subject for the present screening were Ocimum suave, Ocimum lamiifolium, Lippia adoensis, and Ajuga remota. All extracts were observed to possess analgesic properties with varying potencies in tail-flick and hot-plate tests. Analgesic activity, however was not observed with tail-pinch test. The analgesic potencies also varied with concentrations and time after administration. From the present findings, it can be concluded that the extracts of all the plant materials have got analgesic properties with fast onset of action whose mechanisms need to be investigated further., (Copyright 2003 John Wiley & Sons, Ltd.)

Background: There are many traditionally used analgesic plants in Ethiopia. They, however, have not been subject to scientific investigation for their efficacy and safety., Objective: To evaluate both prophylactic and relieving effects of aqueous and ethanol extracts of four traditionally used medicinal plants in Ethiopia., Design: An experimental design in which five group of albino mice weighing 30-35 grams representing positive and negative control, and extract treated groups respectively. The extracts, standard drugs and normal saline were administered into GIT by gavage to evaluate the analgesic effect., Setting: Department of Drug Research at Ethiopian Health and Nutrition Research Institute and Department of Pharmacology at Faculty of Medicine, Addis Ababa university., Methods: Analgesic effects of water and ethanol extracts of four plants were evaluated against distilled water and standard analgesics (morphine and acetylsalicylic acid) with acetic acid induced writhing tests in mice. The four plants used for this screening were Ocimum sauve, Ocimum lamiifolium, Lippia adoensis and Ajuga remota., Results: All extracts of the four plant materials were observed to possess both inhibiting and treatment activities against acetic acid induced pain. Dose related analgesic effect was also observed with all extracts of all plants with different potencies. Ethanol extracts of all the four plant materials were more potent than their water extracts at all dose levels except O. sauve, and L. adoensis whose water extracts seem to be a bit more potent at low dose. The analgesic potencies of both extracts of all the four plants were shown to be less than those of the standard analgesics. Of all the extracts, the ethanol extract of O. lamiifolium was found to be the most potent, while its water extract was the least. Acetic acid induced writhing was relieved with medium dose of both extracts in most cases and with low dose in few. Hundred percent relief was achieved with both standard analgesics at a very low dose., Conclusion: The present study show that all the extracts of all the plant materials have got both inhibiting and relieving effects of pain.

The purpose of this study was to examine the hypoglycaemic effect of the lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10 mg/kg produced a slight and significant decrease in plasma glucose levels in normal rats 6 h after administration and after 3 weeks of treatment. AI reduced plasma glucose levels of streptozotocin diabetic rats from 337+/-9.3 to 102.2+/-17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral administration of AI to streptozotocin diabetic rats significantly decreased the plasma glucose levels after 1 week of treatment (112+/-14.4 mg/dl at 1 week vs 337+/-9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased thereafter and showed a rapid normalisation after 1 week of AI treatment. It is concluded that these results demonstrated that the water extract of the whole plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support therefore, its traditional use in diabetes mellitus control.

Volatile sulfur compounds (VS) are generated in the large intestine by the bacterial metabolism of sulfate and sulfur amino acids. VS are potentially harmful to the host. The effect of dietary supplementation of herb extracts on volatile sulfur production in the large intestine of pig was evaluated in this study. The extracts Perilla frutescens (Soyou), Mentha piperita (Peppermint), and Ajuga decumbens (Kiransou) were fed to pigs equipped with a permanent cannula at the cecum. Cecal digesta were sampled and analyzed for ammonia and short-chain fatty acids (SCFA). Sampled digesta were incubated anaerobically either with or without L-methionine for 24 h to estimate volatile sulfur production in vivo. L-Methionine was supplemented to enhance methanethiol (MeSH) production. At the end of the incubation, head space concentrations of volatile sulfur compounds such as hydrogen sulfide (H2S), MeSH, and dimethyl sulfide (DMS) were determined by flame-photometric gaschromatography after the addition of 6 N HCl. Sampled digesta were also subjected to the most probable number estimations for sulfate-reducing bacteria (SRB), sulfide producer from L-methionine, and MeSH producers from L-methionine. All three herb extracts significantly decreased H2S (p<0.05), MeSH (p<0.05), and ammonia (p<0.05) production, but SCFA production was not affected (p>0.05). The number of volatile sulfur-producing bacteria did not vary among groups by the dietary supplementation of these herb extracts. Serial solvent extraction was done on these herb extracts to specify the active fractions that reduce volatile sulfur production. n-Butanol fraction of all three extracts significantly reduced volatile sulfur production in vitro.