Dihydro-furanones from Hyptis species: Chemical correlations and DFT-NMR/ECD calculations for stereochemical assignments.

Dihydro-furanones are bioactive compounds isolated from various plants, marine fungi, and sponges. The present investigation describes the isolation by recycling HPLC and structural characterization by NMR of four previously undescribed 2(5H)-furanones, monticofuranolide A and pectinolides N-P, one phenylpropanoid, rosmarinic acid, and five known flavonoids, in addition to the undescribed natural flavonoid, 2R,3R-dihydrogossipetin or 5,7,8,3',4'-pentahydroxy flavanonol, from collections of H. monticola Mart. ex Benth and Hyptis pectinata (L.) Poit. Chemical correlations, resembling the biogenetic relationship of the isolated 2(5H)-furanones with their 5,6-dihydro-2H-pyran-2-one precursors, were accomplished to confirm their absolute configuration. Density functional theory-NMR/ECD calculations have been used to solve the absolute configuration for this type of compounds.

Influence of the in vitro gastrointestinal digestion on the antioxidant activity of Artemisia gorgonum Webb and Hyptis pectinata (L.) Poit. infusions from Cape Verde.

The phenolic profile and antioxidant activity of Cape Verde's Artemisia gorgonum Webb and Hyptis pectinata (L.) Poit. infusions before and after in vitro simulation of the gastrointestinal digestion were determined. The LC-UV/DAD fingerprinting analysis allowed the identification of 3-O-caffeoylquinic acid, chlorogenic acid, 3,5 dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid and other caffeoylquinic acids derivatives on A. gorgonum infusion, and of caffeoylquinic acid and quercetin derivatives on H. pectinata infusion. Despite some decrease in the chromatographic area of several peaks, no relevant qualitative alterations on the chromatographic profile were observed between the digested and undigested herbal infusions. Results obtained showed a decrease on the antioxidant capacity of both tested herbal infusions after the in vitro digestion. This decrease was more pronounced for H. pectinata than for A. gorgonum and was also more pronounced regarding the radical scavenging capacity than regarding the reducing capacity. After complete digestion the superoxide anion and the DPPH-radical scavenging capacities decreased ≈ 43 and 75% for H. pectinata and ≈ 31 and 70% for A. gorgonum. Despite the observed differences before and after simulated gastrointestinal digestion, both infusions still had antioxidant activity at the end of this process. Thus, the antioxidant potential of A. gorgonum and H. pectinata infusions from Cape Verde, prepared as traditionally used, seems to be kept in some extend throughout the digestive system.

Nanoemulsion Thermoreversible Pluronic F127-Based Hydrogel Containing Hyptis pectinata (Lamiaceae) Leaf Essential Oil Produced a Lasting Anti-hyperalgesic Effect in Chronic Noninflammatory Widespread Pain in Mice.

We evaluated if a nanostructured thermoreversible Pluronic F127-based hydrogel incorporated with Hyptis pectinata leaf essential oil (NE-EOH) produces a long-lasting anti-hyperalgesic effect on chronic muscle pain in an animal model. We induced chronic muscle pain by injecting the gastrocnemius with saline injections. Paw and muscle withdrawal thresholds and motor performance were evaluated after treatment and compared with morphine, diazepam, or vehicle. Naloxone and methysergide administration tested the involvement of opioid and serotonin receptors, respectively. Sites of action in the central nervous system for the NE-EOH were examined by measuring substance P (SP) levels in the spinal cord and Fos protein in the brainstem. NE-EOH increased paw and muscle withdrawal thresholds when compared with vehicle but had no effect on motor function. This analgesic effect was reversed by both naloxone and methysergide. NE-EOH decreased elevated substance P levels and reduced Fos-labeled neurons in the spinal cord and increased the number of Fos-labeled neurons in the periaqueductal gray (PAG), nucleus raphe magnus (NRM), and locus coeruleus (LC). NE-EOH was shown to produce a lasting anti-hyperalgesic effect. It uses opioid and serotonin receptors, activates brainstem inhibitory pathways, and reduces the release of excitatory neurotransmitters in the spinal cord and is a substance with potential to be used in the treatment of noninflammatory pain conditions. Graphical Abstract.

Hyptis pectinata gel prevents alveolar bone resorption in experimental periodontitis in rats

Hyptis pectinata (L.) Poit., Lamiaceae, is an aromatic, abundant and broadly used plant species in Sergipe to treat oral and gastrointestinal pain and inflammation. The aim of the present study was to analyze the relation between periodontitis and changes in the corporal mass and alveolar bone structure after induction of experimental periodontal disease in rat treated or not treated with H. pectinata gel at 5% (GS5%) and 10% (GS10%), comparing their effects with doxycycline gel at 10% (D10%, positive control), vehicle gel (negative control) and a group with experimental periodontal disease, but non-treated. The gels were locally applied in the gingival region immediately after the experimental periodontal disease induction by ligature (3×/day, 11 days). Bone destruction was determined through clinical exam, histopathological analysis and cone beam computed tomography of the experimental animals (n = 36). After 11 days of periodontitis induction, all groups that received ligature presented a decrease in the corporal mass, except to the naïve group (without experimental periodontal disease) (p < 0.05). Computed tomography results have shown healthy bone structure in the group I and bone resorption for the test groups. Histopathological analysis confirmed the healthy bone structure for naïve group animals, while the test groups exhibited bone loss in several degrees. In particular, the non-treated group animals had an intense inflammatory process. When the periodontium of the animals treated with GS10% was histopathologically analyzed, insertion periodontium was preserved. The results for these groups were significantly different of the vehicle group (p < 0.05). According to the results, the gel based in the aqueous extract of H. pectinata at 10% can prevent bone loss in experimental periodontal disease similarly to doxycycline 10%.

Hyptis pectinata: redox protection and orofacial antinociception.

Hyptis pectinata L. Poit, known as 'sambacaitá', is used in Brazil to treat inflammatory and painful disorders. In this study, the antioxidant and orofacial antinociceptive properties of the aqueous extract of H. pectinata leaves (AEPH) were assessed using in vitro and in vivo models. Thus, AEPH reduced the 2,2-diphenyl-1-picrylhydrazyl radical up to 72.10% with an EC50 of 14.56 µg/ml. It also inhibited 40.80% of the lipoperoxidation induced by 2'-azobis (2-amidinopropane) dihydrochloride in the thiobarbituric acid-reactive substances assay. The orofacial antinociceptive activity was evaluated in mice pre-treated with AEPH (100, 200 and 400 mg/kg, p.o.) and morphine (5 mg/kg, i.p.), which received afterwards formalin- (20 µl, 2% solution, s.c.), glutamate- (40 µl, 25 mM, s.c.) and capsaicin- (20 µl, 2.5 µg, s.c.) to induce orofacial nociception. AEPH at all doses reduced (p < 0.001) the nociceptive response in the first (43-62%) and second (47-80%) phases of the formalin test. Besides, the effect of AEPH (400 mg/kg) was not changed in the presence of naloxone (1.5 mg/kg, i.p.), an opioid antagonist. AEPH significantly inhibited mice face rubbing for capsaicin (23-69%, p < 0.05) and glutamate (48-77%, p < 0.001) at all doses. The findings suggested the AEPH has peripheral and central antinociceptive activities, which are not related to opioid receptors.

Effects of the aqueous extract from Hyptis pectinata leaves on rodent central nervous system / Efeitos do extrato aquoso das folhas da Hyptis pectinata sobre o sistema nervoso central de roedores

The effects of the aqueous extract (AE) from Hyptis pectinata leaves was studied on rodent central nervous system (CNS). Pharmacological screening, open field, forced swimming, apomorphine-induced hypothermia, elevated plus maze and thiopental-induced sleep tests were used in male and female Swiss mice and Wistar rats. The AE was admnistered orally in single doses 30 minutes before each test. In the screening test the AE (400 mg/kg, p.o., n =3) decreased the frequency of grooming behavior. In the open field test it decreased the amount of time rats spent grooming (AE400: 51.3 ± 8.8, q = 5.513, P < 0.01, n = 10), similarly to diazepam (control: 107.3 ± 14.2; diazepam: 15.4 ± 4.3, q = 9.049, P < 0.001, n = 10). In the forced swimming test the AE (400 mg/kg) decreased the immobility time (con: 181.3 ± 7.2 s; imip: 91.6 ± 8.9 s, q = 7.958, P < 0.001; AE400: 111.6 ± 14.5 s, q = 6.193, P < 0.001, n = 9), indicating a possible antidepressive effect. This was confirmed in the apomorphine-induced hypothermia model where the extract (200 mg/kg) antagonized the apomorphine effect (AE200: -0.27 ºC, q = 5.588, P < 0.001, n = 10), similarly to imipramine (imipramine: 5 mg/kg) (control: -1.08 ºC; imipramine: 0.02 ºC, q = 7.589, P < 0.001, n = 10). No effect of the AE was detected in the elevated plus maze and in the sleeping time induced by thiopental models. Our results suggest a possible antidepressive effect of the aqueous extract obtained from the leaves of Hyptis pectinata.

Neste trabalho foram estudados os efeitos do extrato aquoso (EA) obtido das folhas da Hyptis pectinata sobre o sistema nervoso central de roedores. Os seguintes modelos experimentais foram utilizados em camundongos, machos e fêmeas, da linhagem Wistar: "screening" farmacológico, campo aberto, nado forçado, hipotermia induzida por apomorfina, labirinto em cruz elevado e tempo de sono induzido por tiopental. O extrato foi administrado por via oral em dose única, 30 minutos antes de cada teste. No "screening" farmacológico o EA (400 mg/kg, p.o., n = 3) diminuiu a freqüência do comportamento de auto-limpeza. No teste do campo aberto o EA diminuiu o tempo gasto em auto-limpeza (AE400: 51,3 ± 8,8, q = 5,513, P < 0.01, n = 10) de maneira similar ao diazepam (control: 107,3 ± 14,2; diazepam: 15,4 ± 4,3, q = 9,049, P < 0.001, n = 10). No teste do nado forçado o EA (400 mg/kg) diminuiu o tempo de imobilidade (con: 181,3 ± 7,2 s; imip: 91,6 ± 8,9 s, q = 7,958, P < 0,001; AE400: 111,6 ± 14,5 s, q = 6,193, P < 0,001, n = 9) indicando um possível efeito antidepressivo. Isto foi confirmado no modelo de hipotermia induzida pela apomorfina onde o EA (200 mg/kg) antagonizou o efeito da apomorfina (AE200: -0,27 ºC, q = 5,588, P < 0,001, n = 10) de maneira similar à imipramina (5 mg/kg) (control: -1,08 ºC; imipramine: 0,02 ºC, q = 7,589, P < 0,001, n = 10). Nenhum efeito do EA foi observado nos testes do labirinto em cruz elevado e do tempo de sono induzido por tiopental. Nossos resultados sugerem um possível efeito antidepressivo do extrato aquoso obtido das folhas da Hyptis pectinata.

Proliferative effect of the aqueous extract of Hyptis pectinata on liver regeneration after partial hepatectomy in rats / Efeito do extrato aquoso da Hyptis pectinata na regeneração hepática após hepatectomia parcial em ratos

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67 percent partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS:Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submited to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.

OBJETIVO: Este estudo foi realizado com o objetivo de verificar o efeito do extrato aquoso da Hyptis pectinata na regeneração hepática bem como nos níveis das enzimas séricas (AST, ALT e gama-GT) após hepatectomia parcial de 67 por cento em ratos. MÉTODOS: AST, ALT e gama-GT, foram determinadas pelo método cinético utilizando um espectrofotômetro (Modelo E2250-CELM). A regeneração hepática foi avaliada por imunohistoquímica (PCNA). RESULTADOS: O pré-tratamento oral de 100 mg/kg foi realizado durante 4 dias e causou aumento na regeneração hepática O pré-tratamento oral com 200 mg/kg diminuiu significativamente os níveis de AST quando comparado com o grupo submetido ao pré-tratamento com água destilada. As demais enzimas avaliadas não apresentaram diferenças quando comparadas entre os grupos estudados. CONCLUSÃO: O presente estudo mostra que o extrato aquoso da Hyptis pectinata, numa concentração de 100 mg/kg possui alguma atividade biológica estimulando a regeneração hepática e causando também um leve efeito hepatoprotetor numa concentração de 200 mg/kg.

Morphological, agronomical and pharmacological characterization of Hyptis pectinata (L.) Poit germplasm

Several species of the genus Hyptis have presented medicinal characteristics and are frequently indicated to treat gastro intestinal infections, gramps and pain, as well as for skin infections. Three harvests were carried out using six H. pectinata accessions, and the following characteristics were evaluated: plant height, canopy diameter, leave length (L) and width (W), L/W relation and dry weight of leaves and stem. The accession SAM006 have presented highest leave dry matter yield when the three harvests were summed. The aqueous leaf extracts of the same six H. pectinata accessions were tested for anti-edematogenic effect using the carrageenin-induced rat paw edema at doses of 200, 400 and 600 mg/kg. The extracts administered orally had a significant anti-edematogenic effect. The dose of 200 mg/kg of accessions SAM004 and SAM005 had a stronger effect reducing the edema by 19.6 percent and 15.4 percent, respectively. Similar results were obtained using higher dosages of the aqueous extract of the accessions SAM002, SAM003 and SAM006. It can be concluded that the accessions SAM004, SAM005 and SAM006 are promising genotypes for a plant breeding program that aims the development of a cultivar with highest leave yielding and anti-edematogenic effect.

Efeito do extrato aquoso da Hyptis pectinata sobre a proliferação de hepatócitos após hepatectomia parcial

OBJECTIVE: The use of medicinal plants has increased worldwide. Therefore, it is necessary to know their possible effects in order to establish their correct use on human beings. Taking it into account, the objective of this study was to assess the effects of the aqueous extract of Hyptis pectinata leaves, popularly known as "sambacaitá" or "canudinho", on liver regeneration after partial hepatectomy in rats. METHODS: Ten rats were divided into 2 groups: HP group, which underwent 67% hepatectomy after 4 days of distilled water administration; and HP100 group, which was submitted to partial hepatectomy and oral administration of 100 mg/kg of the aqueous extract of Hyptis pectinata for the same period of time. All animals were sacrificed 24 hours after the surgical procedure. Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: The hepatic regeneration index was significantly increased in HP100 group (p 0.05). CONCLUSIONS: The present study shows that the aqueous extract of Hyptis pectinata leaves can stimulate liver regeneration at 100 mg/kg.

OBJETIVO: O uso de plantas medicinais tem aumentado mundialmente. Então, é necessário saber seus possíveis efeitos a fim de estabelecer seu uso correto em seres humanos. Dessa forma, neste trabalho se propôs a estudar os efeitos do extrato aquoso das folhas da Hyptis pectinata, popularmente conhecida como "sambacaitá" ou "canudinho", sobre a regeneração hepática após hepatectomia parcial em ratos. MÉTODOS: Dez ratos foram divididos em 2 grupos: grupos HP, que foi submetido à hepatectomia de 67% após 4 dias de administração de água destilada; e o grupo HP100, que foi submetido à hepatectomia parcial e administração oral de 100 mg/kg do extrato aquoso da Hyptis pectinata pelo mesmo período de tempo. Todos os animais foram sacrificados 24 horas após o procedimento cirúrgico. A regeneração foi analisada através do método de imuno-histoquímica PCNA, usando o anticorpo monoclonal PC-10. RESULTADOS: O índice de regeneração hepática estava significativamente elevado no grupo HP100 (p 0,05). CONCLUSÕES: O presente estudo mostra que o extrato aquoso das folhas da Hyptis pectinata pode estimular a regeneração hepática na concentração de 100 mg/kg.

Efeitos do extrato aquoso da hyptis pectinata sobre a regeneração hepática após hepatectomia parcial de 70%: resultados preliminares

The use of medicinal plants has strongly increased by the world population. The objetive of this study is to assess the effects of the aqueous extract of Hyptis pectinata leaves, popularly known as "sambacaitá" or "canudinho", on liver regeneration after 70% partial hepatectomy. Twenty four rats were divided into 4 groups: group OS, submitted to sham operation and oral administration of distilled water during 4 days; group OSD200, also submitted to sham operation and ingestion of 200 mg of extract/Kg of animal for the same period of time; group HP, which underwent 70% hepatectomy after 4 days of distilled water administration; and group HPD200, which underwent 70% hepatectomy after 4 days of oral administration of 200 mg of extract/Kg of animal. Alkaline phosphatase, total bilirubin and the serum level of aminotransferases were measured and state III of mitochondrial respiratory activity was assessed. Group OSD200, when compared to OS, presented significant decrease of alcaline fosfatase. Group HPD200, when compared to HP, showed statistically significant decrease of AST level and state III respiratory process.

O uso de plantas medicinais tem aumentado bastante na população mundial. O objetivo desta pesquisa é avaliar os efeitos do extrato aquoso das folhas da Hyptis pectinata, popularmente conhecida como "sambacaitá" ou "canudinho", sobre a regeneração hepática após hepatectomia parcial de 70%. Foram utilizados 24 ratos, divididos em 4 grupos: grupo OS, em que se realizou operação simulada e aplicação oral de água destilada por 4 dias; grupo OSD200, também submetido à laparotomia com manipulação do fígado e aplicação de 200 mg de extrato/Kg de animal durante o mesmo período; grupo HP, hepatectomizado a 70% após 4 dias de aplicação por via oral de água destilada; e grupo HPD200, hepatectomizado a 70% após 4 dias de administração de 200 mg extrato/Kg de animal. Foram dosadas fosfatase alcalina, bilirrubina total e as aminotransferases e estudou-se o estado III da função mitocondrial. O grupo OSD200, quando comparado ao OS, apresentou redução significativa da fosfatase alcalina. O grupo HPD200, em comparação ao HP, teve redução estatisticamente significativa no nível da AST e do estado III da função mitocondrial.