PeerJ Preprints: Pharmacologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=6300Pharmacology articles published in PeerJ PreprintsThe occurrence of pharmaceutical waste in different parts of the world: A scoping reviewhttps://peerj.com/preprints/279512019-09-102019-09-10Kim Yun JinMuhammad Shahzad Aslam
Pharmaceutical waste in our ecosystem is the huge burden for our future generations, especially in developing countries. It can be in every place even in drinking water after water treatment. It was observed the presence of over the counter drugs such as ibuprofen, naproxen, acetaminophen and antibiotic such as sulfamethoxazole, trimethoprim, erythromycin the most in the environment. Among all result, Carbamazepine which is known to treat epilepsy was found the most in the environment when the results were compiled from different parts of the world due to its low biodegradable properties. The current article is focused on the occurrence of pharmaceutical waste in the last eight years (January 2010- July 2018) published research work.
Pharmaceutical waste in our ecosystem is the huge burden for our future generations, especially in developing countries. It can be in every place even in drinking water after water treatment. It was observed the presence of over the counter drugs such as ibuprofen, naproxen, acetaminophen and antibiotic such as sulfamethoxazole, trimethoprim, erythromycin the most in the environment. Among all result, Carbamazepine which is known to treat epilepsy was found the most in the environment when the results were compiled from different parts of the world due to its low biodegradable properties. The current article is focused on the occurrence of pharmaceutical waste in the last eight years (January 2010- July 2018) published research work.Antinociceptive and antioxidant activities of methanolic extract of leaves of Azadirachta indica in vivohttps://peerj.com/preprints/278472019-08-062019-08-06Akash S MaliMahesh B ThoratDhairysheel M GhadgeKumodini A NikamShraddha D SawantFarida ShaikhNayana M VhatkarSwapnja ShindeKavyshree D DhongadeMunaf A Tamboli
Background: Azadirachta indica (Neem) is a communal plant of Meliaceae family called Neem Or Kadunimb in Maharashtra, India Neem stated anti-inflammatory through regulation of proinflammatory enzyme activities with COX and LOX enzyme. Previous studies show that Azadirachta Indica (neem) and its chief constituents play essential role in anticancer management via the modulation of different molecular pathways including NF- κ B, p53, PI3K/Akt, Bcl-2, pTEN and VEGF. Many parts of the plant are traditionally used in the treatment of various pharmacological action, the analgesic activity of Neem Seed Oil has already reported but Neem Leaves. Methods: The antinociceptive activity of Azadirachta Indica Leaves (AZIL) was examined using heat-induced-mechanical (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 50,100, and 200 mg/kg doses. ATP-sensitive K+ channel pathway, cyclic guanosine monophosphate (cGMP) pathway and involvement of opioid system was also tested using glibenclamide, methylene blue and naloxone/morphine respectively. The methanolic extract of leaves of A.Indica was assessed by using different in vitro antioxidant models of screening like scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical. Results: AZIL showed antinociceptive activity and antioxidant activity. In both hot plate and tail immersion tests AZIL significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract repressed the number of abdominal writhing. Similarly, AZIL produced substantial dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplanar injection of formalin. As well, AZIL also expressively withdrawn cinnamaldehyde-induced pain and the glutamate-induced pain in mice. It was also proved that pretreatment with naloxone significantly reversed the antinociception produced by AZIL in mechanical tests signifying the involvement of opioid system in its effect. Furthermore, administration of methylene blue, enhanced AZIL induced antinociception while glibenclamide, an ATP-sensitive K+ channel antagonist, could not converse antinociceptive activity induced by AZIL. Conclusion: Based on the results of the present study it can be said that AZIL keeps significant antinociceptive activity which acts in both central and peripheral mechanisms.
Background: Azadirachta indica (Neem) is a communal plant of Meliaceae family called Neem Or Kadunimb in Maharashtra, India Neem stated anti-inflammatory through regulation of proinflammatory enzyme activities with COX and LOX enzyme. Previous studies show that Azadirachta Indica (neem) and its chief constituents play essential role in anticancer management via the modulation of different molecular pathways including NF- κ B, p53, PI3K/Akt, Bcl-2, pTEN and VEGF. Many parts of the plant are traditionally used in the treatment of various pharmacological action, the analgesic activity of Neem Seed Oil has already reported but Neem Leaves. Methods: The antinociceptive activity of Azadirachta Indica Leaves (AZIL) was examined using heat-induced-mechanical (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 50,100, and 200 mg/kg doses. ATP-sensitive K+ channel pathway, cyclic guanosine monophosphate (cGMP) pathway and involvement of opioid system was also tested using glibenclamide, methylene blue and naloxone/morphine respectively. The methanolic extract of leaves of A.Indica was assessed by using different in vitro antioxidant models of screening like scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical. Results: AZIL showed antinociceptive activity and antioxidant activity. In both hot plate and tail immersion tests AZIL significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract repressed the number of abdominal writhing. Similarly, AZIL produced substantial dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplanar injection of formalin. As well, AZIL also expressively withdrawn cinnamaldehyde-induced pain and the glutamate-induced pain in mice. It was also proved that pretreatment with naloxone significantly reversed the antinociception produced by AZIL in mechanical tests signifying the involvement of opioid system in its effect. Furthermore, administration of methylene blue, enhanced AZIL induced antinociception while glibenclamide, an ATP-sensitive K+ channel antagonist, could not converse antinociceptive activity induced by AZIL. Conclusion: Based on the results of the present study it can be said that AZIL keeps significant antinociceptive activity which acts in both central and peripheral mechanisms.The protective effect of nicotinamide riboside against age-induced hepatic disease in micehttps://peerj.com/preprints/277052019-05-062019-05-06Xue HanXiaogang BaoQi LouXian XieShasang ZhouGuojun Jiang
Background & Aims. Aging is one of the key triggers of non-alcoholic fatty liver disease (NAFLD). Yet, the pathomechanism of the age-associated NAFLD is not fully understood. Nicotinamide adenine dinucleotide (NAD), an ubiquitous coenzyme, has beneficial effects on aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of age-induced NAFLD. Methods. NR supplied food (2.5g/kg food) was applied to aged mice for three months. Changes of body weight, food intake, hepar weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammation infiltrated. Results. NR significantly reduced fat pat mass, lipid content and AST in aged mice, but didn't modify in terms of body weight, food intake, hepar weight and ALT in aged mice. Given normal chow, aged mice displayed decline of NAD concentration. In aged mice model, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis (Masson's trichrome staining and TGF-β staining) were observed in liver. In addition, Kupffer cells accumulated and pro-inflammatory cytokines expression were more aggravated in hepatic tissues. Whereas, NR administration completely corrected these NAFLD phenotypes and inflammation infiltrated in liver. Conclusion. NR has benefits on age-associated lipid accumulation and hepatic steatosis, and the oral uptake of NR may be a promising strategy to prevent the progression of NAFLD.
Background & Aims. Aging is one of the key triggers of non-alcoholic fatty liver disease (NAFLD). Yet, the pathomechanism of the age-associated NAFLD is not fully understood. Nicotinamide adenine dinucleotide (NAD), an ubiquitous coenzyme, has beneficial effects on aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of age-induced NAFLD. Methods. NR supplied food (2.5g/kg food) was applied to aged mice for three months. Changes of body weight, food intake, hepar weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammation infiltrated. Results. NR significantly reduced fat pat mass, lipid content and AST in aged mice, but didn't modify in terms of body weight, food intake, hepar weight and ALT in aged mice. Given normal chow, aged mice displayed decline of NAD concentration. In aged mice model, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis (Masson's trichrome staining and TGF-β staining) were observed in liver. In addition, Kupffer cells accumulated and pro-inflammatory cytokines expression were more aggravated in hepatic tissues. Whereas, NR administration completely corrected these NAFLD phenotypes and inflammation infiltrated in liver. Conclusion. NR has benefits on age-associated lipid accumulation and hepatic steatosis, and the oral uptake of NR may be a promising strategy to prevent the progression of NAFLD.Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of ratshttps://peerj.com/preprints/276472019-04-112019-04-11Shangfu XuAnling HuLu XieJiajia LiuQin WuJie J Liu
Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by Western-blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, 5 nuclear receptors, and 4 phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders.
Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by Western-blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, 5 nuclear receptors, and 4 phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders.Physically acting products for head lice – the end of the beginninghttps://peerj.com/preprints/274122018-12-052018-12-05Ian F Burgess
Treatment of head louse infestation has evolved from widespread use of neurotoxic insecticides that have been extensively affected by resistance since the mid-1990s into the use of so-called physically acting treatments. It is widely believed that physically acting products are effectively “resistance proofed” because they do not act to inhibit any particular physiological mechanism and most have some kind of occlusive effect on the target organism. Over the past 20 years various new active materials have been utilized ranging from natural oils, synthetic oils, through to surfactants both as excipients and active substances. Relatively few of these products have been adequately tested clinically and, of those that have, there is now some indication that they are less effective than when first introduced. The question therefore arises whether lice can become resistant to these physically acting products. Only adequate testing both in the laboratory and in clinical trials can determine their real effectiveness and claiming efficacy based on the presence of a named chemical rather than demonstrated activity may result in acquired resistance to these types of product also.
Treatment of head louse infestation has evolved from widespread use of neurotoxic insecticides that have been extensively affected by resistance since the mid-1990s into the use of so-called physically acting treatments. It is widely believed that physically acting products are effectively “resistance proofed” because they do not act to inhibit any particular physiological mechanism and most have some kind of occlusive effect on the target organism. Over the past 20 years various new active materials have been utilized ranging from natural oils, synthetic oils, through to surfactants both as excipients and active substances. Relatively few of these products have been adequately tested clinically and, of those that have, there is now some indication that they are less effective than when first introduced. The question therefore arises whether lice can become resistant to these physically acting products. Only adequate testing both in the laboratory and in clinical trials can determine their real effectiveness and claiming efficacy based on the presence of a named chemical rather than demonstrated activity may result in acquired resistance to these types of product also.Comparing enzyme activity modifier equations through the development of global data fitting templates in Excelhttps://peerj.com/preprints/30942018-08-062018-08-06Ryan Walsh
The classical way of defining enzyme inhibition has obscured the distinction between inhibitory effect and the inhibitor binding constant. This article examines the relationship between the simple binding curve used to define biomolecular interactions and the standard inhibitory term (1+([I]/Ki)). By understanding how this term relates to binding curves which are ubiquitously used to describe biological processes, a modifier equation which distinguishes between inhibitor binding and the inhibitory effect, is examined. This modifier equation which can describe both activation and inhibition is compared to standard inhibitory equations with the development of global data fitting templates in Excel and via the global fitting of these equations to simulated and previously published datasets. In both cases, this modifier equation was able to match or outperform the other equations by providing superior fits to the datasets. The ability of this single equation to outperform the other equations suggests an over-complication of the field. This equation and the template developed in this article should prove to be useful tools in the study of enzyme inhibition and activation.
The classical way of defining enzyme inhibition has obscured the distinction between inhibitory effect and the inhibitor binding constant. This article examines the relationship between the simple binding curve used to define biomolecular interactions and the standard inhibitory term (1+([I]/Ki)). By understanding how this term relates to binding curves which are ubiquitously used to describe biological processes, a modifier equation which distinguishes between inhibitor binding and the inhibitory effect, is examined. This modifier equation which can describe both activation and inhibition is compared to standard inhibitory equations with the development of global data fitting templates in Excel and via the global fitting of these equations to simulated and previously published datasets. In both cases, this modifier equation was able to match or outperform the other equations by providing superior fits to the datasets. The ability of this single equation to outperform the other equations suggests an over-complication of the field. This equation and the template developed in this article should prove to be useful tools in the study of enzyme inhibition and activation.The effect of postoperative oral antibiotic therapy on the incidence of postoperative endophthalmitis after phacoemulsification surgery in dogs. 320 eyes (1997-2006)https://peerj.com/preprints/270912018-08-042018-08-04Amanda T. CorrDaniel A. Ward
Purpose. To assess the effectiveness of postoperative administration of oral antibiotics at reducing the incidence of endophthalmitis following phacoemulsification cataract extraction in dogs.
Methods. Medical records of the University of Tennessee College of Veterinary Medicine were reviewed for cases having undergone phacoemulsification and divided according to whether or not they had received oral antibiotics postoperatively. Records were then evaluated for a diagnosis of endophthalmitis and incidence rates between the group receiving postoperative oral antibiotics and the group not receiving postoperative oral antibiotics were compared.
Results. A total of 185 patients (320 eyes) were identified by the search. 113 patients (197 eyes) were treated with oral antibiotics postoperatively. 72 patients (123 eyes) were not treated with oral antibiotics postoperatively. Two cases of endophthalmitis were identified, with 1 in each group (P>0.05, Fisher’s exact test).
Conclusions. The overall incidence of endophthalmitis in this study was 0.63%. The rate of postphacoemulsification endophthalmitis was unaffected by the postoperative administration of oral antibiotics.
Purpose. To assess the effectiveness of postoperative administration of oral antibiotics at reducing the incidence of endophthalmitis following phacoemulsification cataract extraction in dogs.Methods. Medical records of the University of Tennessee College of Veterinary Medicine were reviewed for cases having undergone phacoemulsification and divided according to whether or not they had received oral antibiotics postoperatively. Records were then evaluated for a diagnosis of endophthalmitis and incidence rates between the group receiving postoperative oral antibiotics and the group not receiving postoperative oral antibiotics were compared.Results. A total of 185 patients (320 eyes) were identified by the search. 113 patients (197 eyes) were treated with oral antibiotics postoperatively. 72 patients (123 eyes) were not treated with oral antibiotics postoperatively. Two cases of endophthalmitis were identified, with 1 in each group (P>0.05, Fisher’s exact test).Conclusions. The overall incidence of endophthalmitis in this study was 0.63%. The rate of postphacoemulsification endophthalmitis was unaffected by the postoperative administration of oral antibiotics.Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood for endotoxin detectionhttps://peerj.com/preprints/269222018-05-102018-05-10Tom MaloneyRyan PhelanNaira Simmons
Horseshoe crabs have been integral to the safe production of vaccines and injectable medications for the past forty years. The bleeding of live horseshoe crabs, a process that leaves thousands dead annually, is an ecologically unsustainable practice for all four species of horseshoe crab and the shorebirds that rely on their eggs as a primary food source during spring migration. Populations of both horseshoe crabs and shorebirds are in decline. This study confirms the efficacy of recombinant Factor C, a synthetic alternative that eliminates the need for animal products in endotoxin detection. Furthermore, our findings confirm that the biomedical industry can achieve a 90-percent reduction in the use of reagents derived from horseshoe crabs by using the synthetic alternative for the testing of water and other common materials used in during the manufacturing process. This represents an extraordinary opportunity for the biomedical and pharmaceutical industries to significantly contribute to the conservation of horseshoe crabs and the birds that depend on them.
Horseshoe crabs have been integral to the safe production of vaccines and injectable medications for the past forty years. The bleeding of live horseshoe crabs, a process that leaves thousands dead annually, is an ecologically unsustainable practice for all four species of horseshoe crab and the shorebirds that rely on their eggs as a primary food source during spring migration. Populations of both horseshoe crabs and shorebirds are in decline. This study confirms the efficacy of recombinant Factor C, a synthetic alternative that eliminates the need for animal products in endotoxin detection. Furthermore, our findings confirm that the biomedical industry can achieve a 90-percent reduction in the use of reagents derived from horseshoe crabs by using the synthetic alternative for the testing of water and other common materials used in during the manufacturing process. This represents an extraordinary opportunity for the biomedical and pharmaceutical industries to significantly contribute to the conservation of horseshoe crabs and the birds that depend on them.Sideritis scardica extracts inhibit aggregation and toxicity of amyloid-β in Caenorhabditis elegans used as a model for Alzheimer's diseasehttps://peerj.com/preprints/34832017-12-222017-12-22Felix HeinerBjörn FeistelMichael Wink
Background. Beyond its traditional uses in the Balkan area, Sideritis scardica (known as Greek mountain tea, Lamiaceae) is currently extensively investigated for its pharmacological activity in the central nervous system. Antidepressant, psychostimulating, cognition-enhancing and neuroprotective properties have been described. In this study, we tested hydroalcoholic extracts of S. scardica for their potential to counteract amyloid-β toxicity and aggregation, which plays a crucial role in the pathogenesis of Alzheimer's disease.
Methods. For this purpose, we have chosen the nematode Caenorhabditis elegans, which is used as a model organism for neurodegenerative diseases. The concentration of different polyphenols in extracts prepared from water, 20, 40, 50, and 70 % ethanol was analysed by HPLC. Additionally, polar and unpolar fractions were prepared from the 40 % ethanolic extract and phytochemically analysed.
Results. Essentially, the contents of all measured constituents increased with the lipophilicity of the extraction solvents. Treatment of transgenic C. elegans strains expressing amyloid-β with the extracts resulted in a reduced number of peptide aggregates in the head region of the worms and alleviated toxicity of amyloid-β, observable through the degree of paralysed animals. The mid-polar extracts (40 and 50 % ethanol) turned out be the most active, decreasing the plaque number by 21 % and delaying the amyloid-β-induced paralysis by up to 3.5 h. The more lipophilic extract fractions exhibited higher activity than the hydrophilic ones.
Discussion. Sideritis scardica extracts demonstrated pharmacological activity against characteristics of Alzheimer's disease also in C. elegans, supporting current efforts to assess its potential for the treatment of cognitive decline. The active principle as well as the mode of action needs to be investigated in more detail.
Background. Beyond its traditional uses in the Balkan area, Sideritis scardica (known as Greek mountain tea, Lamiaceae) is currently extensively investigated for its pharmacological activity in the central nervous system. Antidepressant, psychostimulating, cognition-enhancing and neuroprotective properties have been described. In this study, we tested hydroalcoholic extracts of S. scardica for their potential to counteract amyloid-β toxicity and aggregation, which plays a crucial role in the pathogenesis of Alzheimer's disease.Methods. For this purpose, we have chosen the nematode Caenorhabditis elegans, which is used as a model organism for neurodegenerative diseases. The concentration of different polyphenols in extracts prepared from water, 20, 40, 50, and 70 % ethanol was analysed by HPLC. Additionally, polar and unpolar fractions were prepared from the 40 % ethanolic extract and phytochemically analysed.Results. Essentially, the contents of all measured constituents increased with the lipophilicity of the extraction solvents. Treatment of transgenic C. elegans strains expressing amyloid-β with the extracts resulted in a reduced number of peptide aggregates in the head region of the worms and alleviated toxicity of amyloid-β, observable through the degree of paralysed animals. The mid-polar extracts (40 and 50 % ethanol) turned out be the most active, decreasing the plaque number by 21 % and delaying the amyloid-β-induced paralysis by up to 3.5 h. The more lipophilic extract fractions exhibited higher activity than the hydrophilic ones.Discussion.Sideritis scardica extracts demonstrated pharmacological activity against characteristics of Alzheimer's disease also in C. elegans, supporting current efforts to assess its potential for the treatment of cognitive decline. The active principle as well as the mode of action needs to be investigated in more detail.Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblastshttps://peerj.com/preprints/32272017-10-312017-10-31Toshiaki AraNorio Sogawa
Previously, we revealed that several kampo medicines that are used for patients with excess and/or medium patterns [kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)] reduced prostaglandin (PG)E<2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.
Previously, we revealed that several kampo medicines that are used for patients with excess and/or medium patterns [kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)] reduced prostaglandin (PG)E<2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.