{"id":2875,"date":"2015-05-02T09:20:32","date_gmt":"2015-05-02T09:20:32","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=2875"},"modified":"2020-04-26T05:43:38","modified_gmt":"2020-04-26T05:43:38","slug":"aqueous-extract-of-echium-amoenum-elevate-csf-serotonin-and-dopamine-level-in-depression-rat","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol7no1\/aqueous-extract-of-echium-amoenum-elevate-csf-serotonin-and-dopamine-level-in-depression-rat\/","title":{"rendered":"Aqueous Extract of Echium amoenum Elevate CSF Serotonin and Dopamine Level in Depression rat"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Depression disorder is one of the most common mental illness in the world and became a very important area of research interest in psychopharmacology. Major depressive disorder (MDD) is characterized by a lowered mood. The working mechanism of AD is believed to be either by increased neurotransmission by increased synaptic levels of serotonin, norepinephrine (NE) and dopamine (DA) (monoamines) (1). The increased levels of monoamines were discoveredin the late fifties, when the TCAs and Monoamine oxidase A inhibitors (MAO-I) appeared to effectively treat MDD. This discovery resulted to the monoamine hypothesis: MDD might etiologically be explainedby a deficiency in monoamine neurotransmitters: serotonin (5-HT), NE or DA(2,3).\u00a0 Desire in alternative medicine and plant-derived medications that affect the \u2018mind\u2019 is developing. Self administration of herbal medicines was the most popular alternative treatments to the official medicine. The application of herbal medications is becoming very common by physicians in Europe and Asia and researchers are exploring the traditional remedies to find a fit cure for these \u2018mind affecting diseases\u2019.Moreover, Iranian climate and favored geographical location have contributed to the diversity of medicinal plants.Borage (Echium amoenum) is a wild annual herb that belongs to Boraginaceae family which grows in large parts of Europe, Mediterranean region, and also in parts of Iran (4). The flowers and the leaves of borage are used medicinally in the West and iran for the treatment of Stress, analgesic, anxiolytic, sedative, circulatory heart diseases, pulmonary complaints and other psychiatric illnesses (4-7). Volatile constituents of E.amoenum was extracted by Ghassemi et al, These compounds include octadecane, heptadecane, viridiflorol, alpha cadinen etc (8). Toxic pyrolizidine alkaloids of E. amoenum were separated by Mehrabani et al (9). It has been shown that flavonoids possess mild sedative and anxiolytic effects, the naturally occurring flavonoids and their synthetic derivatives have been revealed to bind selectively to the central benzodiazepine receptors and to us anxiolytic and other benzodiazepine like effects in animals (10).The anxiolytic and antidepressant effect of the flower of Echium amoenum was demonstrated in several experimental studies in mice and human (9,11). Despite the widespread use of E. amoenum as an antidepressant , there are no\u00a0 pharmacological data of\u00a0 antidepressant mechanism of E. amoenum . The aim of the present study was to evaluate effect the aqueous extract of E. amoenum on changes the level of CSF serotonin and dopamine as indicator mood in depression rat.<\/p>\n

Experimental<\/strong><\/p>\n

Plant material an Extraction<\/strong><\/p>\n

An aqueous extract (pH=6) of dried flowers was used in this study. E.amoenum <\/em>flowers were collected from Ilam district, Iran. Flowers of this plant were separated and dried in roomtemperature (22-24 \u00b0C). The plant materials were powdered and exhaustively extracted with distilled water in a Soxhlet apparatus under reduced pressure. After evaporation of the solvent in rotary evaporator and then in oven at 40 \u00b0C, the residue was diluted with salinefor obtain the desire concentration (125 mg\/kg ).<\/p>\n

Animals<\/strong><\/p>\n

The experiment was conducted,using four groups (seven rat each)weighed 250-300g. The animals were kept in a 25\u00b12 \u00b0C temperature with a 12 hr light \/dark cycle and fed with standarddiet and tap drinking water. Animals were randomly divided into 4 groups; control ,depression, control + Echium amoenum and depression+ Echium amoenum,The rats were acclimatized to the laboratory for at least 1 h before\u00a0 oral performing of aqueous extractEchium amoenum(125mg\/kg)and were administrated extraction\u00a0 CSF after two weeks of treatment,The experiments were carried out between 9.00 and 14.00 h. The experimental protocol was approved byof Animal house and\u00a0\u00a0 Ethical Committee at Ilam University of Medical Sciences (IUMS).<\/p>\n

Porsolt swim test for assessment depression <\/strong><\/p>\n

The procedure for the Porsoltforced swim test was as previously reported (Porsolt, LePichon, and Jalfre, 1977). By\u00a0 administrating depression rats with intraperitoneal injection of reserpine-sigma(5mg\/kg) (12) and assessment depression by swimming test, Briefly, rats were placed in a cylindrical container (40 cm deep, 27 cm in diameter) filled with 30 cm of 30\u00b0C water. The amount of time the rats spent swimming or immobile was recorded in a 10-min test. Swimming was defined as movement of the forelimbs and hindlimbs without the front paws breaking the surface of the water. Immobility was recorded when there was an absence of any movement other than that necessary to keep the head andnose above the water (e.g., when rats were floating in a vertical position).<\/p>\n

CSF sampling<\/strong><\/p>\n

The rats were anesthetized with 40 mg kg of sodium thiopental, intrapritonal andplaced in a stereotaxic frameand implanted with a guide cannula which was\u00a0 an insulin syringe (27 gauge 31\/ 20 length by direct puncture of the cisterna magna was drawn CSF (40\u201360\u00a0 micro liter per rat), CSF was collected from each rat (13).<\/p>\n

Neurotransmitters analysis<\/strong><\/p>\n

The level serotonin and dopamine of CSF samples were measured usingthe IBL international GMBH ELISA kit (Germany) and LDN GMBH Kit according to the manufacturer instruction. The procedures for each neurotransmitter is summarized as follows.<\/p>\n

Serotonin ELISA<\/strong><\/p>\n

20 \u03bcL of each Control and sample was pipetted\u00a0 into glass test tubes the 100 \u03bcL of diluted Assay Buffer\u00a0 was added to each tube. Vortex.Then 25 \u03bcL of Acylation Reagent 1 (3 %) Pipetted into each tube. Vortex each tube immediately after pipe ting. Cover tubesIncubated 15 min at 37\u00b0C in a water bath, Then\u00a0 4 mL of diluted Assay Buffer\u00a0 was Pipetted into each tube. Vortex. The all tubes Centrifuged for 10 min at 1500 x g. immediately Prepared samples assayed, The supernatant was stabled for only 1 h at 18-25\u00b0C.<\/p>\n

Dopamine ELISA<\/strong><\/p>\n

In the first 25 \u00b5l of the Enzyme Solution was pipetted into all wells of the Dopamine Microtiter Strips. Then\u00a0 was added 100 \u00b5l of the standards, controls and samples into the appropriate wells incubated for 30 min at RT on a shaker (approx. 600 rpm) and also 50 \u00b5l Dopamine antiserum was added to the wells and the plate covered with adhesive Foil,\u00a0 then incubated for 2 hours at RT on a shaker. 3 times washing content of the wells and discarding followed by using 300 \u00b5l washing buffer. Next stage was added 100 \u00b5l of enzyme conjugate into all wells incubating 30 min at RT on a shaker. After washing, 100 \u00b5l of the substrate was added into all wells and incubated for 20-30 min at RT followed by adding 100 \u00b5l of the stop solution to each well and reading the absorbance of the solution in the wells within 10 minutes, using a micro plate reader set to 450 nm and a reference wavelength between 620 nm and 650 nm.<\/p>\n

Statistical analysis<\/strong><\/p>\n

Results are presented as mean\u00b1S.E.M. ANOVA was used for compare serotonin and dopamine in each group of 7 rat. Normality of data in each group was checked using one sample kolmogroror- simirnov test, Dennett test was performed as a post hoc multiple comparison analysis,P- value <0.05\u00a0 was\u00a0 significantstatistically.<\/p>\n

Results<\/strong><\/p>\n

Effect of <\/strong>Echium<\/strong> amoenum <\/strong>aqueous<\/strong>extract on changes level\u00a0 CSF serotonin<\/strong><\/p>\n

\u00a0<\/em>Figure 1 display, the effect of aqueous extract of Echium amoenumon on changes level\u00a0 CSF serotonin in different groups, ANOVA analysis indicated the differences between various groups (P<0.05), the following analysis with Dunnett- test (Table 1) showed that changes level serotonin in the control\u00a0 group with the depression group\u00a0 and depression group receiving Echium amoenum was statically significant(P<0.05). However, the difference between\u00a0 depression group with depression group receiving Echium amoenum was statically significant (P<0.05). whereas for the other cases, it was not. In tables and figures con equal control, dep (depression) and Ech (Echium amoenum).<\/p>\n\n\n\n
\"Figure<\/td>\nFigure 1: The effect of Echium amoenum aqueous extract on changes level CSF serotonin in different groups.<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 1: The effect of aqueous extract Echium amoenum with dose 125 mg\/kg after two weeks of oral\u00a0 performing on changes level\u00a0 CSF serotonin in different groups. Data are presented as mean values (“S.E.M.) from a group of 7 rat each. P-0.05 compared with control.<\/strong><\/p>\n\n\n\n\n\n\n\n
\u00a0 Dependent Variable\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 J group\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 I group<\/strong><\/td>\nMean<\/strong><\/p>\n

Difference (J-I)<\/strong><\/td>\n

Std. Error<\/strong><\/td>\nSig.<\/strong><\/td>\n<\/tr>\n
 <\/p>\n

 <\/p>\n

CSF serotonin<\/strong><\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/td>\n

Control\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Depression<\/td>\n-8.25714<\/td>\n1.06954<\/td>\n.000<\/td>\n<\/tr>\n
Control\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Depression+Ech<\/td>\n-2.21429*<\/sup><\/td>\n61994.<\/td>\n.004<\/td>\n<\/tr>\n
Control+Ech\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Depression+Ech<\/td>\n-1.25714<\/td>\n61994.<\/td>\n.131<\/td>\n<\/tr>\n
\u00a0<\/strong><\/p>\n

Depression\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Depression+Ech<\/td>\n

-2.65714<\/td>\n.61994<\/td>\n.001<\/p>\n

\u00a0<\/strong><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Effects of Echium amoenumaqueous extract on changes level\u00a0 CSF\u00a0 dopamine<\/strong><\/p>\n

Figure 2 indicate,\u00a0 the effect of aqueous extract of Echium amoenumon on changes level\u00a0 CSF dopamine in different groups, ANOVA analysis indicated the differences between various groups (P<0.05), the following analysis with Dunnett- test (Table2)\u00a0 showed that changes level dopamine in the control group with the depression group was statically significant(P<0.05). However, the difference between depression group with depression group receiving Echium amoenum was statically significant (P<0.05). Whereas for the other cases, it was not.<\/p>\n\n\n\n
\"Figure<\/td>\nFigure 2: The effect of Echium amoenum aqueous extract on changes level\u00a0 CSF dopamine in different groups.<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 2: The effect of aqueous extract Echium amoenum with dose 125 mg\/kg after two weeks\u00a0 of oral\u00a0 performing on changes level\u00a0 CSF dopamine in different groups. Data are presented as mean values (“S.E.M.) from a group of 7 rat each. P-0.05 compared with control.<\/strong><\/p>\n\n\n\n\n\n\n\n
\u00a0 Dependent Variable\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 J group\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 I group<\/strong><\/td>\nMean<\/strong><\/p>\n

Difference (J-I)<\/strong><\/td>\n

Std. Error<\/strong><\/td>\nSig.<\/strong><\/td>\n<\/tr>\n
 <\/p>\n

 <\/p>\n

CSFdopamine<\/strong><\/p>\n

\u00a0<\/strong><\/td>\n

Control\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0Depression<\/td>\n-8.25714<\/td>\n1.06954<\/td>\n.000<\/td>\n<\/tr>\n
 <\/p>\n

Control\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Depression+Ech<\/td>\n

.04286<\/td>\n.04041<\/td>\n.590<\/td>\n<\/tr>\n
Control +Ech\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Depression+Ech<\/td>\n.10000<\/td>\n.04041<\/td>\n.053<\/td>\n<\/tr>\n
Depression\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Depression+Ech<\/td>\n-.20000<\/td>\n.04041<\/td>\n.000<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Discussion and conclusions<\/strong><\/p>\n

Impact of Echium amoenum aqueous extract on rat depression by evolution change level CSF serotonin<\/strong><\/p>\n

The lowering of in brain serotonin cause lower mood and enhancing in irritability or aggressive behaviors but the increasing concentration of serotonin possibly help to develop more constructive social interactions by reducing aggression and increasing dominance(14,15). Altered serotonin metabolism may be a highly magnify interfering factor aggression and suicide behavior in human, because\u00a0 reported earlier that lowering levels of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite cause these behaviors (16). Our finding showed which the level of CSF serotonin increased in depression group and control group treatment by Echium amoenum (Figure 1).<\/p>\n

Impact of Echium amoenum aqueous extract on rat depression by evaluation change level CSF dopamine<\/strong><\/p>\n

The studies revealed that depressive symptoms in schizophrenic patients are accossieted with a decrease in dopamine synthesis(17-19). The finding indicated that DA and DA D2 receptors play magnify role in the reinforcing responses to psycho stimulants in humans (20).The studies Electro physiological demonstrated dopamine responses that consist predominantly of depressions (21).Our finding demonstrated that the level CSF dopamine increased in depression group treatment by Echium amoenum (Figure 2), the results showed that anxiolytic effect of the extract Echium amoenum was most evident in 125 mg\/kg group (6). Petals of E. amoenum have been advocated for its anxiolytic, sedative, anti-inflammatory, demulcent and analgesic effects,\u00a0\u00a0 particularly\u00a0 for common cold, in folk medicine of Iran (4-7).\u00a0Data analysis of the present study showed that the aqueous extract of Echium amoenum (125 mg\/kg) significantly\u00a0 increased the level\u00a0 of CSF serotonin and dopamine. The results suggests that Echium amoenum has effect antidepressant\u00a0 and enhancer mood , in part active\u00a0 with elevating level\u00a0 of CSF serotonin and dopamine as indicators mood. Althught arenot clear contributing mechanisms \u00a0we suggest the researches continue with investigate effect Echium amoenum on changes level norepinephrine, GABA\u00a0 and other neurotransmitters\u00a0 as mood disorders\u00a0 indicators.<\/p>\n

Reference<\/strong><\/p>\n

    \n
  1. Ruhe,H. G., Mason, N. S. & Schene, A. H. 2007. Mood Is Indirectly Related To Serotonin, Norepinephrine And Dopamine Levels In Humans: A Meta-Analysis Of Monoamine Depletion Studies. Molecular Psychiatry, 12, 331-359.<\/li>\n
  2. Booij, L., Van Der Does, A. J. W. & Riedel, W. J. 2003. Monoamine Depletion In Psychiatric And Healthy Populations: Review. Molecular Psychiatry,<\/em> 8,<\/strong> 951-973.<\/li>\n
  3. Hood, S. D., Bell, C. J. & Nutt, D. J. 2005. Acute Tryptophan Depletion. Part I: Rationale And Methodology. Australian And New Zealand Journal Of Psychiatry,<\/em> 39,<\/strong> 558-564.<\/li>\n
  4. Amin, Gh.1991. Popular Medicinal Plants Of Iran. Iranian Research Institute Of Medicinal Plants, Tehran, P. 80.<\/li>\n
  5. Hooper, D., 1937. Useful Plants And Drugs Of Iran And Iraq. Field Museum Of Natural History, Chicago, Usa, P. 115.<\/li>\n
  6. Shafaghi, B., Naderi, N., Tahmasb, L., Kamalinejad, M., 2002. Anxiolytic Effect Of Echium Amoenum In Mice. Iranian Journal Of Pharmaceutical Research 1, 37\u201341.<\/li>\n
  7. Zargari, A., 1996. Medicinal Plants, Vol. 3. Tehran University Publications, Tehran, Pp. 513, 538.<\/li>\n
  8. Ghassemi, A., Sajjadi ,A., Ghannadi ,Mr., Shams- Ardakani, Mehrabani ,M.2003.Volatile Constituents Of A Medicinal Plant Of Iran Echium Amoenum. Daru,11,32\u201333.<\/li>\n
  9. Mehrabani,M.,Ghannadi,A.,Sajjadi,E.,Ghassemi,N.,Shams-Ardakani Mr. 2006.Toxic Pyrrolizidinealkaloids Of Echium Amoenum Fisch. & Mey. Daru,14,122-127.<\/li>\n
  10. Medina,Jh., Viola ,H., Wolfman, C., Marder ,M., Wasowski, C., Calvo, D., Et Al. 1997.Overviewflavonoids: A New Family Of Benzodiazepines Receptor Ligands. Neurochem Res. ,22,419-<\/li>\n
  11. Ranjbar,A.,Khorami,S.,Safarabadi,M.,Shahmoradi ,A., Malekirad, Aa., Vakilian, K., Et Al.2006. Antioxidant Activity Of Iranian Echium Amoenum Fisch & C.A.Mey Flower Decoction In Humans: A Cross-Sectional Before\/After Clinical Trail. Evid Based Complement Altern Med,3,469-473.<\/li>\n
  12. Mehdi, Sayyaha.,Mohammad,Sayyahb.,Mohammad,Kamalinejadc.2006. A Preliminary Randomized Double Blind Clinical Trial On The Efficacy Of Aqueous Extract Of Echium Amoenum In The Treatment Of Mild To Moderate Major Depression . Progress In Neuro-Psychopharmacology And Biological Psychiatry,Volume 30, Issue 1, Pages 166\u2013169.<\/li>\n
  13. Gaylord, De., Curzon, G.1972. Test Of Emotional Behavior In Rats Following Depletion Of Norepinephrine, Of Serotonin, Or Both. Psychopharmacologia, 34,275-88.425.<\/li>\n
  14. Rafael Guimara Es Silva, Dio\u00b4 Genes Santiago Santos, Luiz Augusto Basso,Jean Pierre Oses, Susana Wofchuk, Luis Valmor Cruz Portela,And Diogo Onofre Souza. Purine Nucleoside Phosphorylase Activity In Rat Cerebrospinal Fluid. Neurochemical Research, Vol. 29, No. 10, (2004), Pp. 1831\u20131835.<\/li>\n
  15. Simon,N., Young*., Marco Leyton.2002.The Role Of Serotonin In Human Mood And Social Interaction Insight From Altered Tryptophan Levels. Pharmacology, Biochemistry And Behavior, 71,857\u2013865.<\/li>\n
  16. Wendelien Merens , A.J. ,Willem Van Der Does., Philip Spinhoven.2007. The Effects Of Serotonin Manipulations On Emotional Information Processing And Mood ,Journal Of Affective Disorders, 103 ,43\u201362.<\/li>\n
  17. Brown, Gerald L; Et Al .Aggression, Suicide, And Serotonin: Relationships Of Csf Amine Metabolites. The American Journal Of Psychiatry, Vol 139(6), Jun 1982, 741-746.<\/li>\n
  18. Hietala, J., Syv\u00e4lahti ,E., Vilkman ,H., Vuorio, K., R\u00e4kk\u00f6l\u00e4inen ,V., Bergman, J., Haaparanta ,M., Solin, O., Kuoppam\u00e4ki, M., Eronen, M., Ruotsalainen, U., Salokangas, Rkr .1999.Depressive Symptoms And Presynaptic Dopamine Function In Neuroleptic-Na\u00efve Schizophrenia. Schizophr Res ,In Press.<\/li>\n
  19. Tiihonen, J., Kuoppam\u00e4ki, M., N\u00e5gren, K., Bergman, J., Eronen, E., Syv\u00e4lahti ,E., Hietala, J.1996.Serotonergic Modulation Of Striatal D2 Dopamine Receptor Binding In Humans Measured With\u00a0Positron Emission Tomography. Psychopharmacology, 126, 277\u2013280.<\/li>\n
  20. D\u2019haenen, Ha., Bossuyt ,A. 1994. Dopamine D2 Receptors In Depression Measured With Single Photon Emission Computed Tomography. Biol Psychiatry, 35, 128\u2013132.<\/li>\n
  21. Nora D. Volkow, Gene-Jack Wang, Joanna S. Fowler, Jean Logan, S. John Gatley, Cristopher Wong, Robert Hitzemann, And Naomi R. Pappas. 1999.Reinforcing Effects Of Psychostimulants In Humans Are Associated With Increases In Brain Dopamine And Occupancy Of D2 Receptors1. By The American Society For Pharmacology And Experimental Therapeutics Printed In U.S.A. Jpet, 291,409\u2013415.<\/li>\n
  22. Wolfram Schultz. 2007. Behavioral Dopamine Signals. Trends In Neurosciences Vol.30 No.5.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction Depression disorder is one of the most common mental […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-2875","post","type-post","status-publish","format-standard","hentry","category-vol7no1"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/2875","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=2875"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/2875\/revisions"}],"predecessor-version":[{"id":33111,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/2875\/revisions\/33111"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=2875"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=2875"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=2875"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}