Characterization of the cold and hot natures of raw and processed Rehmanniae Radix by integrated metabolomics and network pharmacology

BackgroundThe processing of Chinese materia medica (CMM) is one of the characteristics and advantages of traditional Chinese medicine (TCM). Occasionally, the processing of CMM might reverse the cold/hot nature of CMM. For example, the nature of raw Rehmanniae Radix (RR) is cool, while the processed Rehmanniae Radix (PR) by steaming is hot. Because the cold/hot nature of CMM is defined by the body's response to CMMs, a metabolomics approach, allowing the monitoring of the fluctuation of endogenous metabolites related to an exogenous stimulus, might be an ideal tool to uncover the cold/hot nature of different forms of Rehmanniae Radix.PurposeAn integrated strategy combining metabolomics and network pharmacology was applied to illuminate the different natures of raw and processed Rehmanniae Radix.Study designMice were orally administered RR and PR once daily for ten days. The entire metabolic changes in the plasma of mice were profiled by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS). Furthermore, network pharmacology analysis was performed to identify the underlying targets related to iridoids that significantly changed during the processing.ResultsThe metabolomics analysis results demonstrated a clear separation of the metabolic phenotypes among the control, RR and two PR groups in both the positive and negative modes. Nine lysophosphatidylcholines (LysoPCs), LysoPC (16:0), LysoPC (18:2), LysoPC (18:1), LysoPC (22:6), LysoPC (20:2), LysoPC (18:0), LysoPC (16:1), LysoPC (20:4) and LysoPC (20:5), that decreased in the RR-treated group, but increased in the PR-treated group, were identified to be potential biomarkers related to the natures of RR and PR. The network pharmacology results indicated that four iridoids in Rehmanniae Radix, 8-epiloganic acid, 6-O-p-coumaroyl ajugol, 6-O-p-hydroxybenzoyl ajugol and ajugol, might play important roles in the different natures of raw and processed Rehmanniae Radix.ConclusionsThere might be a strong connection between the cold/hot nature of different forms of Rehmanniae Radix and LysoPC metabolism. This study offers new insight into the cold/hot nature of Rehmanniae Radix.     

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

Cold hypersensitivity is a serious clinical problem, affecting a broad subset of patients and causing significant decreases in quality of life. The cold plantar assay allows the objective and inexpensive assessment of cold sensitivity in mice, and can quantify both analgesia and hypersensitivity. Mice are acclimated on a glass plate, and a compressed dry ice pellet is held against the glass surface underneath the hindpaw. The latency to withdrawal from the cooling glass is used as a measure of cold sensitivity.Cold sensation is also important for survival in regions with seasonal temperature shifts, and in order to maintain sensitivity animals must be able to adjust their thermal response thresholds to match the ambient temperature. The Cold Plantar Assay (CPA) also allows the study of adaptation to changes in ambient temperature by testing the cold sensitivity of mice at temperatures ranging from 30 °C to 5 °C. Mice are acclimated as described above, but the glass plate is cooled to the desired starting temperature using aluminum boxes (or aluminum foil packets) filled with hot water, wet ice, or dry ice. The temperature of the plate is measured at the center using a filament T-type thermocouple probe. Once the plate has reached the desired starting temperature, the animals are tested as described above.This assay allows testing of mice at temperatures ranging from innocuous to noxious. The CPA yields unambiguous and consistent behavioral responses in uninjured mice and can be used to quantify both hypersensitivity and analgesia. This protocol describes how to use the CPA to measure cold hypersensitivity, analgesia, and adaptation in mice.     

《伤寒论》中甘草方剂应用特点及配伍应用的规律探讨

《伤寒论》中霍乱病篇、六经病篇以及瘥后劳复病篇会广泛应用甘草,多用于寒证、表证、虚实夹杂病证及虚证等,少用于实证、热证中与湿热证中,攻逐、急下、涌吐、收敛固涩类方证及清利湿热中不用。本研究通过分析甘草的品种产地、性味归经、功效主治、《伤寒论》关于甘草方剂的应用、甘草配伍情况、应用禁忌、甘草用于表里寒热虚实病证治疗分析以及甘草和其它药物配伍相关性,探讨伤寒论》中甘草方剂应用特点及配伍应用的规律,以期能够实现甘草的最佳应用效果。     

Effects of fermented rooibos (Aspalathus linearis) on adipocyte differentiation

Rooibos (Aspalathus linearis) contains a rich complement of polyphenols, including flavonoids, considered to be largely responsible for its health promoting effects, including combatting obesity. The purpose of this study was to examine the effect of fermented rooibos hot water soluble solids on in vitro adipocyte differentiation by using differentiating 3T3-L1 adipocytes. Hot water soluble solids were obtained when preparing an infusion of fermented rooibos at “cup-of-tea” strength. The major phenolic compounds (>5 mg/g) were isoorientin, orientin, quercetin-3-O-robinobioside and enolic phenylpyruvic acid-2-O-β-d-glucoside. Treatment of 3T3-L1 adipocytes with 10 μg/ml and 100 μg/ml of the rooibos soluble solids inhibited intracellular lipid accumulation by 22% (p < 0.01) and 15% (p < 0.05), respectively. Inhibition of adipogenesis was accompanied by decreased messenger RNA (mRNA) expression of PPARγ, PPARα, SREBF1 and FASN. Western blot analysis exhibited decreased PPARα, SREBF1 and AMPK protein expression. Impeded glycerol release into the culture medium was observed after rooibos treatment. None of the concentrations of rooibos hot water soluble solids was cytotoxic, in terms of ATP content. Interestingly, the higher concentration of hot water soluble solids increased ATP concentrations which were associated with increased basal glucose uptake. Decreased leptin secretion was observed after rooibos treatment. Our data show that hot water soluble solids from fermented rooibos inhibit adipogenesis and affect adipocyte metabolism, suggesting its potential in preventing obesity.     

Traditional Chinese medicines differentially modulate the gut microbiota based on their nature (Yao-Xing)

BackgroundProperty theory is a unique principle guiding traditional Chinese medicine (TCM) that classifies various TCMs into four natures (hot, warm, cool, and cold) to reflect their medical actions on the human body. Despite successful application for thousands of years, characterizing the nature of medical TCMs by modern physiological indicators remains a challenge.PurposeIn this study, we investigated the potential relationship between the nature of TCMs and their modulation of the gut microbiota.Study DesignWe selected twelve TCMs with hot, warm, cool, or cold natures that possess antidiarrheal effects. Their aqueous extracts were orally administered to C57BL/6 mice at a clinical dose for 4 weeks. The gut microbiota was measured by 16S rRNA-based metagenomics, and the correlation between microbial composition/function and TCM nature was analyzed.ResultsAntidiarrheal TCMs with different natures showed distinct impacts on the gut microbiota. Hot-natured TCMs had no influence on the gut microbiota, warm-natured TCMs had a moderate influence, cool-natured TCMs had a strong influence, and cold-natured TCMs substantially changed the structure of the gut microbial community. The abundance of Anaerotruncus, Tyzzerella and Ruminiclostridium steadily increased, while that of Ruminococcaceae_UCG-010, Parasutterella and Bifidobacterium continuously decreased as the herbal nature turned from cold to hot. Microbiome functional prediction for Cluster of Orthologous Groups (COG) of proteins and Kyoto Encyclopedia of Genes and Genomes (KEGG) categories showed that colder TCMs imposed a stronger influence on microbial functional repertoires. Specifically, the abundance of ABC transporters, key bacterial proteins involved in nutrient absorption and drug resistance, was gradually decreased by colder TCMs.ConclusionOur results demonstrated that the nature of TCMs could be reflected by their modulation of gut microbes. Cold TCMs may exert their antidiarrheal effects, at least partially, by modulating the gut microbiota, while hot TCMs may alleviate dysentery in other ways.     

Cold acclimation induces freezing tolerance via antioxidative enzymes, proline metabolism and gene expression changes in two chrysanthemum species

Cold acclimation is necessary for chrysanthemum to achieve its genetically determined maximum freezing tolerance, but the underlying physiological and molecular mechanisms are unclear. The aim of this study was to discover whether changes in antioxidative enzymes, proline metabolism and frost-related gene expression induced by cold acclimation are related to freezing tolerance. Our results showed that the semi-lethal temperature (LT₅₀) decreased from ?7.3 to ?23.5 °C in Chrysanthemum dichrum and ?2.1 to ?7.1 °C in Chrysanthemum makinoi, respectively, after cold acclimation for 21 days. The activities of SOD, CAT and APX showed a rapid and transient increase in the two chrysanthemum species after 1 day of cold acclimation, followed by a gradual increase during the subsequent days and then stabilization. qRT-PCR analysis showed that the expression levels of some isozyme genes (Mn SOD, CAT and APX) were upregulated, which was consistent with the SOD, CAT and APX activities, while others remained relatively constant (Fe SOD and Cu/Zn SOD). P5CS and PDH expression were increased under cold acclimation and the level of P5CS presented similar trends as proline content, indicating proline accumulation was via P5CS and PDH cooperation. Cold acclimation also promoted DREB, COR413 and CSD gene expression. The activities of three enzymes and gene expression were higher in C. dichrum than in C. makinoi after cold acclimation. Our data suggested that cold-inducible freezing-tolerance could be attributed to higher activity of antioxidant enzymes, and increased proline content and frost-related gene expression during different periods.     

基于ESDA的西北太平洋柔鱼资源空间热点区域及其变动研究

以西北太平洋(150°E—160°E、38°N—45°N)柔鱼Ommastrephes bartramii为研究对象,以2007和2010年鱿钓渔业的原始点位数据为基础,利用常规统计和探索性空间数据分析(ESDA)中的全局空间自相关分析方法,对西北太平洋柔鱼资源空间分布及其变动进行了研究。结果表明,西北太平洋柔鱼资源呈现较强的聚集分布特征,但不同空间位置差异较大。利用GIS和ESDA的局部自相关方法进行了柔鱼资源热冷点空间分布的制图,结果显示2007年研究区存在3个显著的热点和1个冷点,2010年与之存在较为明显的差异,具有1个热点和4个冷点。变化检测分析表明,两个年份间出现1个热点区域和1个冷点区域未发生变化,另有2个区域从2007年热点变成2010年冷点;此外,非热冷点之间的变动在研究区占据了主导地位。景观指数分析表明,研究区柔鱼资源热冷点格局的复杂性和自相似性并不高,但其异质性和聚集性非常强,且整体性和凝聚度均很高。分析认为,2007年西北太平洋柔鱼渔区的形成受温度和海流的影响,近一半作业渔区产量相对较高,但并未充分保证空间热点的大面积形成,空间热点和冷点分布面积大致相当;2010年整个西北太平洋柔鱼渔场受亲潮势力影响,空间热点较为集中、空间冷点较多且分散。     

Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety evaluation in mice

The analgesic activity of Porcellio laevis Latreille, Rhizoma Corydalis, and Radix Cynanchi Paniculati have been reported in recent years. A new formula named Jia-Yuan-Qing pill (JYQP) is therefore created by combining the three herbs at 9:7:7 ratio according to traditional Chinese theories. The present study aims to evaluate the effect of JYQP as a novel painkiller in various models. Acute toxicity test was applied to evaluate the safety of JYQP. Acetic-acid-induced writhing, hot plate test, formalin test, and naloxone-pretreated writhing test were employed to elaborate the analgesic activity of JYQP and its possible mechanism. A bone cancer pain mouse model was performed to further assess the effect of JYQP in relieving cancer pain. Test on naloxone-precipitated withdrawal symptoms was conduct to examine the physical dependence of mice on JYQP. Data revealed that JYQP reduced writhing and stretching induced by acetic acid; however, this effect could not be blocked by naloxone. JYQP specifically suppressed the phase II reaction time in formalin-treated mice; meanwhile, no analgesic effect of JYQP in hot plate test was observed, indicating that JYQP exerts analgesic activity against inflammatory pain rather than neurogenic pain. Furthermore, JYQP could successfully relieve bone cancer pain in mice. No physical dependence could be observed upon long-term administration in mice. Collectively, our present results provide experimental evidence in supporting clinical use of JYQP as an effective and safe agent for pain treatment.     

Comparison between partial ulnar and intercostal nerve transfers for reconstructing elbow flexion in patients with upper brachial plexus injuries

The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p.) for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS), super-oxide anion content (markers of oxidative stress) and total calcium levels were measured. Vincristine administration was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia. Furthermore, vincristine administration was also associated with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o.) and its saponin rich fraction (100 and 200 mg/kg p.o.) for 14 days significantly attenuated vincristine-induced neuropathic pain along with decrease in oxidative stress and calcium levels. It may be concluded that Ocimum sanctum has ameliorative potential in attenuating chemotherapy induced-painful neuropathic state, which may be attributed to decrease in oxidative stress and calcium levels. Furthermore, saponin rich fraction of Ocimum sanctum may be responsible for its noted beneficial effect in neuropathic pain in rats.     

Swamps,springs and diatoms: wetlands of the semi-arid Bogoria-Baringo Rift,Kenya

Lakes Bogoria and Baringo lie in a semi-arid part of the Kenya Rift Valley between 0° 15′–0° 30'N and 36° 02′–36° 05′E. Nevertheless, the area around these lakes contains numerous wetland systems that have been formed: along lake shorelines; along faults where hot, warm and cold springs have developed; and along river systems that cross the rift floor. Six major types of wetland are recognized: Proximal Hot Springs; Hot Spring Marshes; Blister Wetlands; Typha and Cyperus papyrus Swamps; Floodplain Marshes; Hypersaline Lake Littoral Wetlands; and Freshwater Lake Littoral Wetlands. These show significant variability in terms of geomorphic setting, water chemistry, temperature, plant communities and diatom floras. They are variously dominated by macrophytes, such as Cyperus laevigatus, Typha domingensis and Cyperus papyrus. In some cases macrophytes are absent. In hot spring settings and in hypersaline lake littoral zones bacterial mats are common. Although absent in some samples, diatoms occur in at least parts of all of the wetlands, varying in diversity, abundance and species composition. Canonical correspondence analysis indicates that diatom floras show a close relationship with pH, temperature, and specific conductivity, with other environmental variables such as Si and nitrate being of secondary importance. Common diatoms include: Anomoeoneis sphaerophora var. guntheri, Navicula tenella, N. cuspidata, and Nitzschia invisitata in hot springs, where diversity is generally low and abundance is variable. Other wetland types contain distinctive diatom floras that variously include: Fragilaria brevistriata, Gomphonema parvulum, Navicula tenelloides, Nitzschia communis, N. latens, N. sigma, Rhopalodia gibberula, and Stauroneis anceps.     

Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in mice

Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of phytol metabolites in vivo in females and less so in males. Concomitantly, dietary phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic phytol metabolism than FABP1.     

Restoration of Dlk1 and Rtl1 Is Necessary but Insufficient to Rescue Lethality in Intergenic Differentially Methylated Region (IG-DMR)-deficient Mice

In the Dlk1-Dio3 imprinted domain, an intergenic differentially methylated region (IG-DMR) regulates the parental allele-specific expression of imprinted genes. The maternally inherited deletion of IG-DMR (IG-DMR^(−/+)) results in perinatal lethality because of the overexpression of paternally expressed genes and repression of maternally expressed noncoding RNAs (ncRNAs), including Gtl2. To better understand the possible contribution of paternally expressed genes to the lethality, we attempted to rescue the lethality of IG-DMR^(−/+) mutants by restoring the paternally expressed genes. Because the paternally inherited Gtl2 deletion (Gtl2^(+/−)) induced a decrease in the expression of paternally expressed genes, we crossed female IG-DMR heterozygous mice and male Gtl2 heterozygous mutant mice. The resultant IG-DMR^(−/+)/Gtl2^(+/−) double mutant mice had normal expression levels of paternally expressed genes, and none of them showed perinatal lethality; however, most mice showed postnatal lethality with decreased expression of the maternally expressed ncRNAs. Thus, we inferred that paternally expressed genes are necessary for perinatal survivability and that maternally expressed ncRNAs are involved in postnatal lethality.     

Thermal plasticity in the invasive south American tomato pinworm Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae)

South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is a devastating invasive global insect pest of tomato, Solanum lycopersicum (Solanaceae). In nature, pests face multiple overlapping environmental stressors, which may significantly influence survival. To cope with rapidly changing environments, insects often employ a suite of mechanisms at both acute and chronic time-scales, thereby improving fitness at sub-optimal thermal environments. For T. absoluta, physiological responses to transient thermal variability remain under explored. Moreso, environmental effects and physiological responses may differ across insect life stages and this can have implications for population dynamics. Against this background, we investigated short and long term plastic responses to temperature of T. absoluta larvae (4th instar) and adults (24–48 h old) from field populations. We measured traits of temperature tolerance vis critical thermal limits [critical thermal minima (CT_min) and maxima (CT_max)], heat knockdown time (HKDT), chill coma recovery time (CCRT) and supercooling points (SCP). Our results showed that at the larval stage, Rapid Cold Hardening (RCH) significantly improved CT_min and HKDT but impaired SCP and CCRT. Heat hardening in larvae impaired CT_min, CCRT, SCP, CT_max but not HKDT. In adults, both heat and cold hardening generally impaired CT_min and CT_max, but had no effects on HKDT, SCP and CCRT. Low temperature acclimation significantly improved CT_min and HKDT while marginally compromising CCRT and CT_max, whereas high temperature acclimation had no significant effects on any traits except for HKDT in larvae. Similarly, low and high temperature acclimation had no effects on CT_min, SCPs and CT_max, while high temperature acclimation significantly compromised adult CCRT. Our results show that larvae are more thermally plastic than adults and can shift their thermal tolerance in short and long timescales. The larval plasticity reported here could be advantageous in new envirnments, suggesting an asymmetrical ecological role of larva relative to adults in facilitating T. absoluta invasion.     

Bacterial composition of microbial mats in hot springs in Northern Patagonia: variations with seasons and temperature

Seasonal shifts in bacterial diversity of microbial mats were analyzed in three hot springs (39?C68 °C) of Patagonia, using culture-independent methods. Three major bacterial groups were detected in all springs: Phyla Cyanobacteria and Bacteroidetes, and Order Thermales. Proteobacteria, Acidobacteria and Green Non-Sulfur Bacteria were also detected in small amounts and only in some samples. Thermophilic filamentous heterocyst-containing Mastigocladus were dominant Cyanobacteria in Porcelana Hot Spring and Geyser, and Calothrix in Cahuelmó, followed by the filamentous non-heterocyst Leptolyngbya and Oscillatoria. Bacteroidetes were detected in a wide temperature range and their relative abundance increased with decreasing temperature in almost all samples. Two Meiothermus populations with different temperature optima were found. Overall, fingerprinting analysis with universal bacterial primers showed high similarities within each hot spring despite differences in temperature. On the other hand, Cahuelmó Hot Spring showed a lower resemblance among samples. Porcelana Hot Spring and Porcelana Geyser were rather similar to each other, possibly due to a common geological substrate given their geographic proximity. This was even more evident with specific cyanobacterial primers. The different geological substrate and the seawater influence in Cahuelmó might have caused the differences in the microbial community structure with the other two hot springs.     

Effects of outdoor temperature on changes in physiological variables before and after lunch in healthy women

Previous studies of autonomic nervous system responses before and after eating when controlling patient conditions and room temperature have provided inconsistent results. We hypothesized that several physiological parameters reflecting autonomic activity are affected by outdoor temperature before and after a meal. We measured the following physiological variables before and after a fixed meal in 53 healthy Japanese women: skin temperature, systolic and diastolic blood pressure, salivary amylase, blood glucose, heart rate, and heart rate variability. We assessed satiety before and after lunch using a visual analog scale (100 mm). We recorded outdoor temperature, atmospheric pressure, and relative humidity. Skin temperature rose significantly 1 h after eating (greater in cold weather) (P?=?0.008). Cold weather markedly influenced changes in diastolic blood pressure before (P?=?0.017) and after lunch (P?=?0.013). Fasting salivary amylase activity increased significantly in cold weather but fell significantly after lunch (significantly greater in cold weather) (P?=?0.007). Salivary amylase was significantly associated with cold weather, low atmospheric pressure, and low relative humidity 30 min after lunch (P?P?=?0.001). The decreased low frequency (LF)/high frequency (HF) ratio, increased Δ LF/HF ratio, and increased Δ salivary amylase activity imply that cold outdoor temperature is associated with dominant parasympathetic activity after lunch. Our results clarify the relationship between environmental factors, food intake, and autonomic system and physiological variables, which helps our understanding of homeostasis and metabolism.     

Ingestion of a Cold Temperature/Menthol Beverage Increases Outdoor Exercise Performance in a Hot,Humid Environment

Purpose

A recent laboratory study demonstrated that the ingestion of a cold/menthol beverage improved exercise performance in a hot and humid environment during 20 km of all-out cycling. Therefore, the aim of this study was to determine whether the ingestion of cold water/ice-slurry with menthol would improve performance in hot and humid outdoor conditions.

Methods

Ten trained males completed three trials of five blocks consisting of 4-km cycling and 1.5-km running. During warm-up, every block and recovery, the athletes drank 190 ml of aromatized (i.e., with 0.05 mL of menthol) beverage at three temperatures: Neutral (ambient temperature) (28.7°C±0. 5°C), Cold (3.1°C±0.6°C) or Ice-slurry (0.17°C±0.07°C). Trial time, core temperature (T_co), heart rate (HR), rate of perceived exertion (RPE), thermal sensation (TS) and thermal comfort (TC) were assessed.

Results

Ice-slurry/menthol increased performance by 6.2% and 3.3% compared with neutral water/menthol and cold water/menthol, respectively. No between-trial differences were noted for T_co, HR, RPE, TC and TS was lower with ice-slurry/menthol and cold water/menthol compared with neutral water/menthol.

Conclusion

A low drink temperature combined with menthol lessens the performance decline in hot/humid outdoor conditions (i.e., compared with cold water alone). Performances were better with no difference in psycho-physiological stress (T_co, HR and RPE) between trials. The changes in perceptual parameters caused by absorbing a cold/menthol beverage reflect the psychological impact. The mechanism leading to these results seems to involve brain integration of signals from physiological and psychological sources.     

Search for anticonvulsant and analgesic active derivatives of dihydrofuran-2(3H)-one

A series of derivatives of dihydrofuran-2(3H)-one (γ-butyrolactone, GBL) was synthesized and tested for anticonvulsant, neurotoxic and analgesic activity. In the anticonvulsant screening 10 lactones were effective in the maximal electroshock test (MES) at the highest doses (300 and 100 mg/kg, 0.5 h, ip, mice). Statistical analysis showed correlation between the anticonvulsant activity and relative lipophilicity parameters determined by experimental and computational methods (R_M0, C log P and M log P). Preliminary antinociceptive evaluation of selected derivatives revealed strong analgesic activity. The majority of the tested compounds showed high efficacy in animal models of acute pain (hot plate and writhing tests) and strong local anesthetic activity (modified tail immersion test). The obtained ED₅₀ values were comparable with such analgesics as acetylsalicylic acid and morphine.