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Cover page of the Journal of Health Sciences


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 2  |  Page : 109-114

Concept of oja vis -a -vis endoplasmic reticular function: An approach to decode the holistic view


Department of Dravyaguna, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India

Date of Web Publication17-Jan-2016

Correspondence Address:
Anagha Vishwas Ranade
Department of Dravyaguna, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5006.174238

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  Abstract 

Background: In Ayurveda, Oja, being one of the most distinctive concepts is a factor of prime importance related to vitality. Ayurveda depicts the definition, types (Para, Apara); site (Hridaya- Heart, sarvashariravyapi - presence in cellular level), quantity (vindu-in drops), function (bala-vitality) and its derangement etiology etc. of Oja. Various researchers based on their own ideas have given its modern parlance with immunity and stem cell etc.
Objective: To decipher the fundamental concept of Oja vis-ΰ-vis endoplasmic reticular function.
Material and Methods: A critical analysis of information on Oja from available Ayurvedic literatureand endoplasmic reticular function form modern Physiology texts.
Result: 'Endoplasmic reticulum(ER)' is a multifunctional membranous organelle forming a network in the whole body and is responsible for lipid biosynthesis, calcium storage and protein folding and processing. Etiological factors of Ojadushti (dysfunction) are (Abhighata-may be environmental stress), (shoka-mental stress), (shrama-physical stress, etc) which share similarity with stressors that disrupt function of ER ultimately leading to ER stress causing lifestyle disorders. Achieving cellular homeostasis is now being emphasized in the management of various diseases, in conventional medicine. The cellular homeostasis is dependent largely onproper folding of proteins where as in proper folding results into accumulation of misfolded proteins ultimately enhancing cellular death. Scientific reports on vayathapanaherbs like Amalaki, Punarnava, Guduchi etc. to alleviate ER stress can be give an evidence to correlate the ER with Oja.
Conclusion: The present hypothesis gives an insight to decipher a novel concept of Oja and its relation with Endoplasmic reticulum.

Keywords: Endoplasmic reticulum, Oja, vayasthapana


How to cite this article:
Ranade AV, Acharya R. Concept of oja vis -a -vis endoplasmic reticular function: An approach to decode the holistic view. Indian J Health Sci Biomed Res 2015;8:109-14

How to cite this URL:
Ranade AV, Acharya R. Concept of oja vis -a -vis endoplasmic reticular function: An approach to decode the holistic view. Indian J Health Sci Biomed Res [serial online] 2015 [cited 2019 Dec 13];8:109-14. Available from: http://www.ijournalhs.org/text.asp?2015/8/2/109/174238


  Background Top


In Ayurveda, Oja, being one of the most distinctive concepts is a factor of prime importance related to vitality. Oja is regarded to be the purest part of the seven dhatus and is referred to as Bala by Acharya Sushruta[1] the innate quality that produces resistance against many diseases. Besides this, Acharyas have stated in detail about the types, peculiar characteristics, functions, and the etiology behind its dysfunction that leads in total disruption of the normal homeostasis of the body which is sometimes fatal. This concept persuades to think in deep about the role of Oja to the cellular level.

In the recent past, various researchers based on their own ideas, have given its modern parlance with immunity and stem cell, etc. The views differ in explanation of Oja namely it is quoted to be a factor related to immunity in the physiology text of Dr. Ranjitraya Desai; [2] whereas referred as a part of vitamins, albumin, glycogen, internal secretions of testicles, ovary, prostatic secretions by Dr. Ghanekar. [3] These aspects focus on only certain physiological aspects of Oja. However, still, the location wise variation and types of Oja, the role of Bala, etc., are untouched. A thorough deciphering of each and every aspect of Oja, as reported in the classical texts, is necessary.

In spite of thorough research on the etiology aspects of a disease, scientists still ponder over the concept of vitality. Past scientific researchers have highlighted the role of different cellular organs in controlling bodily functions. Role of endoplasmic reticulum (ER), Golgi apparatus etc., have been reported and recently, more emphasis is being laid on their participation in maintaining cellular homeostasis which is in close line with normal Oja function. On a deep thought, an organelle named "ER" is present in every cell and regulates cellular homeostasis. Oja is debated not to be a dhatu as it does not possess nutritional property (poshaka guna).[4] The ER too participates only in the maintenance of homeostasis. In the present article, an attempt to correlate its typical location and types and functions with Oja has been done by making a thorough review on Oja about its constitution, functions, etc., from various classical texts and recent texts related to Ayurveda.

A critical analysis of ER functions has been carried out from various e-journal articles and scientific papers followed by the study of probable correlation of Oja vis-a-vis ER as regards to its types, prime location, physiological functions, and pathological functions, etc.


  Results Top


Oja

Oja
has been attributed with two synonyms that is, Bala (overall strength), Prakrit Shleshma, in the classical texts of Ayurveda. [5] Based on the prime site of function, Oja has been divided into two types, namely, Para Oja and Apara Oja. Para Oja is present in heart and its function is mainly associated with the heart. Apara Oja is present in Ojovahi dhamanya[6] and functions all over the body. The presence of Oja during the formation of zygote after fertilization and also during the formation of heart and in organogenesis has also been highlighted by Chakrapani, a celebrated commentator of Charak Samhita[7] [Table 1]. Etiology of Ojo dushti is mentioned by Sushruta Samhita[8] with the effects resulting in three stages of pathogenesis namely Visramsa, Vyapanna, Kshaya; last being fatal.

Endoplasmic reticulum

The ER is a vital organelle present in all eukaryotic cells. It consists of interconnected, branching membranous tubules, vesicles, and cisternae that provide a distinct subcellular compartment with a number of functions. The rough ER is studded with ribosomes on its outer surface and plays a key role in protein synthesis and secretion. Smooth ER is central to the synthesis of fatty acids and phospholipids, assembly of lipid bilayers, metabolism of carbohydrates, and regulation of calcium homeostasis [9] [Table 1]. One of the significant functions of ER is protein folding and processing.
Table 1: Characteristics of Oja and ER

Click here to view



  Discussion Top


Prime site

Para Oja is located in the heart. In case of ER, a specialized type of sarcoplasmic reticulum (SR) is present predominantly in the heart having the function of calcium metabolism regulation in cardiac myocytes. [10] Even, in relation to the presence of Oja in cardiogenesis. [11] It is postulated that the shuttle of free Ca2 + in and out of the ER is essential for a proper generation of pacemaker activity during early cardiogenesis and fetal life. [12] The ER also has been to possess a role in the formation of zygote from oocyte, the necessary RNA molecules are directed by ER through a novel protein Vera (VgLE binding and ER association). Thus, ER has a role in organogenesis. [13]

For Apara Oja, Ojovahi dhamanya can be possibly correlated with the cisterns and membranes (MAMs) of ER as it refers the network and channels present in all eukaryotic cells through which the ER functions.

Physiological functions

Kritsna dhatu Sneha

Oja
has been quoted as Kritsna dhatu Sneha.[14] On closely reading between the lines, we can correlate this with the lipid biogenesis function of ER. [15] Unctuous component of all dhatus can thus be probably the de novo (new) lipid component synthesis and inter MAM transport which is a prime function of ER. Lipids, especially phospholipid bilayer is important for MAM integrity and also aids in absorption of certain components. Here, we see that, "Prakrit Shleshma0" synonym also suits for functional action of ER as the Shleshma deals with maintaining stability at cellular level.

Pranayatanam-Agnishomiya

Sushruta
[16] has termed Oja to be Pranayatana[17] and the purest form derived from Shukra dhatu which is further referred as Teja and then Bala, the innate immunity. Dalhana (commentator of Sushruta Samhita) [18] is of the opinion that Pranayatana is an entity which possess Agni as well as Soma.[19] In case of varied functions of ER, we see it depicts both stability and synthetic functions. A scientific reference suggests that the mitochondria-associated ER MAM is a specialized sub-domain of the ER MAM that regulates ER-mitochondria communications. The importance of inter-organelle communication in the innate immune response to virus infection and in the pathophysiology of neurodegenerative/neurodevelopmental disorders is coming up. [20] Thus, the role of ER in immunity satisfies even the complex dual Agni-Soma nature of Oja.

Bala

Sthiraupachitmamsata
(well-developed muscle tissue and mass as well as the upachita sharira) is one of the functions of Bala as per Sushruta.[21] ER; both smooth and rough are important in case of protein synthesis, carbohydrate and lipid metabolism, exchange of ions, and detoxification. These processes are needed to maintain the overall equilibrium. Among the smooth ER, a modified part of it named SR present in skeletal muscle has a role in coupling of excitation and contraction, [22] which helps in proper muscle contraction. The SR of heart differs structurally from skeletal muscle.

Sarva Cheshtasu Apratighatatva[21] (clearing hindrances for normal function of physiological processes) can be correlated with the proper protein translocation, folding, and quality control function of ER [23] thereby ensuring normal cellular function.

Dysfunction

Causal similarity

Oja dushti
: Ojo dushti is quoted in Sushruta Samhita[24] to be caused due to Abhighat (infliction of injury), Kshaya, Kopa, Shoka, etc.

Endoplasmic reticulum stress


The inavailability of oxygen (hypoxia) or glucose (hypoglycemia), radiation, acidosis, calcium levels, the redox milieu, energy levels (modulated by hypoxia and hypoglycemia), and other factors can impact and disturb proper functioning of the ER, resulting in ER stress, and impacting protein folding in the lumen of the ER. [25]

On close look at the ER stress etiology, we can possibly correlate Abhighata with irradiation, Kshaya with Hypoxia, Kopa with oxidation, acidosis.

Manifestation of disease process

Effect of Ojo dushti (Oja dysfunction)

The effect of Ojo dushti has been described by Sushruta in three stages [26] among which last is fatal. In the first stage (i.e., Visramsa), he has stated symptoms such as Sandhivishlesha, Gatrasadana, Dosha chyavana, kriyasannirodha, etc., In the second stage (Vyapanna), symptoms such as immobility in the body, Vatashopha (acute inflammation), discolouration of skin, lassitude, tandra, nidra while in the third stage (i.e., Kshaya) symptoms such as fainting, muscle wasting, stupefaction, delirium, and death.

Stages of ER stress response

Under ER stress conditions, unfolded proteins accumulate in the ER, and this eventually induces the perturbation of cellular activities. The fate of the cell is either survival or apoptosis in ER stress conditions. This results in accumulation of misfolded proteins in the cell triggering the self-protective mechanism in the cell itself named unfolded protein response (UPR). [27] This response of eukaryotic cells consists of three different mechanisms [Figure 1].

In mammals, the UPR signaling pathway is initiated by three ER MAM-associated sensors: (1) Activating transcription factor-6, (2) inositol-requiring transmembrane kinase/endoribonuclease, and (3) double-stranded RNA-dependent protein kinase - like eukaryotic initiation factor 2 alpha (PERK).

First, under ER stress initial signaling contributes to adaptive changes as shown in the figure out of which some are moved on to the recovery stage. Some are adapted to stress but result into disorders and the third and last apoptosis of cells.
Figure 1: The image states the correlation of three stages of endoplasmic reticulum stress with the three types of Oja dysfunction

Click here to view


If we closely compare the three stages of Oja dushti, the severity increase and last in Kshaya, symptoms such as Maranam, Moha, Mamsakshaya, etc., represent the disorders resulting due to apoptosis [Figure 1]. These symptoms are in correlation with neurodegeneration and chronic disorders and last stages of cancer. This resultant UPR resulting in wrong signaling to cellular level can be correlated with the following verse: [28]

'Teja samiritam tasmata visramsayati dehina' which means the vitiated teja component along with Vata due to the causative factors like Abhighat etc., produce Visramsa resulting in Kriyasannirodha. We can interpret that wrong signaling is the possible abnormal Vata function resulting in mitochondrial and ER dysfunctions and UPR. These being sites of synthesis (mainly proteins) can be considered as Teja predominant. Thus, the levels of ER stress correspond to three stages of Ojo dushti which worsen further leading to death.

Diseases due to Oja dysfunction

Diabetes

Oja Kshaya
that is, (Apara Oja) in Prameha has been reported by Acharya Charak.[29] Being Apara Oja Kshaya, it renders the disease to be nonfatal. In contemporary medicine, we get evidences where diabetes is caused due to ER stress. This is the major area where research is being focused. Accumulating evidence suggests that ER stress plays a role in the pathogenesis of diabetes, contributing to pancreatic β-cell death, and insulin resistance. [30]

Viability issue of fetus in 8 th month

During the 8 months of pregnancy, Ayurveda states that the fetus in case, if delivered, is not viable as the Oja is not stable. [31] In the modern medicine, the viability issue is said to be due to respiratory distress because of fetal lung immaturity. [32] The production of surfactant starts around 28-30 weeks (in ER), when lung is immature and hence, birth of infants in this period leads to infant respiratory distress syndrome.

Again evidences show that the ER has a central role in the production of surfactant proteins which are responsible for maintaining surface tension in lung and preventing lung collapse. Any sort of mutation in the ER function leads to ER stress leading to UPR thereby hampering surfactant mechanism and fetal distress is set in due to immaturity of fetal lung. [33] In Ayurveda, antenatal care [34] includes Ojaskar dravyas such as ghee, milk, butter which may have a role to facilitate ER function and prevent ER stress because all these possess natural lipid and steroidal source which are major in formation of the thin film during maintenance of surface tension. Besides this, glucocorticoids are often started in 7 th month if fetal lung immaturity is observed.

Cancer

In case of cancer, many physicians of Ayurveda consider Oja Kshaya and hence, switch the treatment to enhance Oja by prescribing Rasayana drugs. Herein, we find the role of chronic ER stress in inducing carcinogenesis. The reports on usage of medicinal plants suggest that these plants develop ER stress in cancerous cells but not in normal cells. Thus, their action seems to be target-specific. We can say that in treating cancer, Oja Kshaya is caused in cancer cells by creating ER stress in them thereby protecting the Oja function of normal cells.

A good illustration is of curcumin induced apoptosis in cancer cells. [35]

Cardiovascular diseases

In case of SR stress, it disrupts the calcium function thereby leading to abnormal contraction and signaling in myocytes which is the root cause of cardiac dysfunction. [36] Pressure overload is thought to activate ER stress-mediated apoptosis in the mouse myocardium and ER stress was shown to contribute to ischemia-induced apoptosis in cultured cardiac myocytes. In cardiac myocytes, the ER MAM network is potentially more expansive than many other cell types, due to the role played by the SR in contractile calcium handling. The potential overlap in function between the SR and the ER in terms of protein synthesis and folding, as well as ER stress and mTOR signal transduction, suggests that the SR and ER MAM system is a macro-organelle that plays critical roles in cardiac myocyte contraction, growth, and metabolism, all of which are dominant contributors to myocardial function. [37] Thus, in Oja Kshaya, we can say that the Bala Kshaya and Maranam correspond to the cellular apoptosis and this can be fatal in case of heart.

Other diseases

ER stress roles are also reported in production of many neurodegenerative disorders such as Alzheimers, Parkinson's disease, etc.; also in atherosclerosis, hypertension, obesity, and many more chronic disorders.

Some evidences of role of medicinal plants in alleviation of endoplasmic reticulum stress

Punarnava: (Boerhaavia diffusa Linn.) Reduces excessive calcium influx which caused due to ER stress. In Ayurveda, it is often used to manage edema in CVDs. [38]

Shalaparni: (Desmodium gangeticum L. DC) significantly brought the activities of the mitochondrial respiratory enzymes and some sarcoplasmic enzymes to a near normal level and thereby reduces calcium overload.

Guduchi: (Tinospora cordifolia L.).

Berberine exerts anti-apoptotic effect and improves cardiac functional recovery following myocardial I/R via activating AMPK thereby alleviating ER stress. [40]

Yashtimadhu: (Glycyrrhiza glabra L.).

Glycyrrhizin was found to have anti-apoptotic effects on induced acute liver injury in rats through the inhibition of JNK1/2 and p38 MAPK phosphorylation and inactivation of the CHOP protein, thereby reducing ER stress. [41]

Triphala: A study on triphala has also been reported in alleviation of ER stress. [42]

On keen observation, most of them belong to the Vayasthapana category. All these are rasayana drugs.


  Conclusion Top


Oja and ER possess functional similarity. ER stress can be used as a pathological marker for Ojo dushti. The Vayasthapana[43] drugs are thus concerned with the correction of early aging of cells due to environmental stressors and can be used as Ojaskar dravyas in the management of Oja dysfunction.

For further scope, the various Rasayana drugs, Jivaniya, and Vayasthapana category drugs can be screened to assess their function in the alleviation of ER stress thereby proving the Ojaskara activity. The enzymes used to assess endoplasmic reticular stress can be used for further assessing Ojo dysfunction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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