Anti-Post-Traumatic stress Potential of Strawberry (Fragaria) and Carissa carandas Leaves: A Review

 

Jaymala Arun Kumawat¹, Birendra Shrivastava², Vaishali M. Mute³

¹Research scholar, Jaipur National University, Jagtpura Jaipur, Rajasthan.

²Director, Jaipur National University, Jagtpura Jaipur, Rajasthan.

³Assistant Professor, JSPMS Rajushri Shau College of Pharmacy and Research, Thathawade, Pune.

 

ABSTRACT:

Post-traumatic stress disorder (PTSD) is the least apperceived mental disorder globally, associated with trauma and stressor cognate disorder. Administration of synthetic drugs on a constant schedule may lead to adverse events and other complications. Thus, Anti-PTSD medications require novel herbal pharmacological therapy. Recently, Anti-PTSD activity of Carissa carandas (CC) and Fragaria leaves (FL) has been demonstrated. Both are valuable bioresource for a range of health-related applications since they accommodate as a source of bioactive compounds with powerful antioxidant potential higher than in other berries. They possess faculty to cross the blood-brain barrier and chelate transition metal ions as well as forage pathological amounts of reactive oxygen and nitrogen species. For neuro-pathophysiology and pharmacological evaluations, pharmacologically different animal models of PTSD have been developed. Animal models are a prominent approach to learn PTSD without requiring to use of actual victims. A genuine effort has been taken in this article which provides the clear and cosine worldwide proven anti-PTSD potential of CC and Fl. The objective behind this article is to new vision to present and future scientists, researchers, industries, and regulatory bodies on the potential anti-PTSD potential of CC and Fl for the betterment of society by highlighting clinical and pre-clinical studies which contributed to support the concept. Any outcome in a model can be extrapolated to humans, giving scientists a better picture of what to anticipate mechanistically and in treatment response. Thus, CC and FL have wide application in mental disorders precisely in PTSD and as being herbal formulation, it has lesser adverse effects as compared to synthetic drugs.

 

 

1. INTRODUCTION:

Out of many mental diseases, Post-traumatic stress disorder (PTSD) is one of the most common major health concerns worldwide even if still poorly recognized and not well treated¹. PTSD is a severe psychiatric condition and a traumatic event having the capacity to provoke fear, helplessness, or horror in response to the threat of injury or death². In this condition several symptoms overlap with major depressive disorders, anxiety disorders and substance abuse; this may contribute to diagnostic confusion and under diagnosis³.

 

There are four characteristic features of PTSD. These include exposure to a traumatic event, re-experiencing of the traumatic event, avoidance and increased arousal⁴. PTSD often develops in response to one or more traumatic events such as deliberate acts of interpersonal violence, severe accidents, disasters or domestic action. Those at risk of PTSD include survivors of war and torture, of accidents and disasters, and of violent crime (for example, physical and sexual assaults, sexual abuse, bombings and riots), refugees, women who have experienced traumatic childbirth, people diagnosed with a life-threatening illness, and members of the armed forces, police and other emergency personnel⁵. The symptoms of PTSD are readily identifiable by a primary care physician. Because there is substantial overlap between the symptoms of PTSD and those of depression and other anxiety disorders, however, the diagnosis is easily missed unless specific inquiries are made about the occurrence of a traumatic event ⁶.

 

Figure-1 Worldwide regulatory and non-regulatory statics on Post-traumatic stress disorder (PTSD).

 

Figure-2, A= Fragaria plant, B= Fragaria leaf, C= Carissa carandas Plant, and D= Carissa Carandas Leaf.

 

 

There is a long history of herbal use as anti-post-traumatic therapy in the future also there is a need for herbal anti-post-traumatic therapy and the validated anti-post-traumatic potential of many plant remedies that are available in the literature showing controlled analyses in healthy and diseased animals as well as humans in the last ten years ⁷.

 

2. Fragaria Leaves:

As shown above, in the figure-3 strawberry plant (Fragaria ananassa D.), a member of the Rosaceae family, is the most extensively grown fruit plant in the world ⁰⁸. It is a low-growing, herbaceous perennial plant of height about 5 -20 cm with a fibrous root system and a crown from which arise basal leaves. The leaves are small to medium in size, average 4-5 centimeters in width. The shape of the leaf is flat and is rounded at each end with parallel sides ^09.. Margins of the leaf are serrated or with saw-toothed edge lobed and with hairy petiole ^10.

 

Traditionally and ethno medicinally Fragaria leaf (FL) is used for numerous treatments like ^11-12:

·       Digestion: FL is known to assist inadequate metabolism in the human body. Leaf when utilized in a tea relieves the symptoms of gastrointestinal stress and aids in metabolism.

·       Arthritis: Caffeic acid, a chemical substance in FL helps in relieving pain related to arthritis by decreasing the inflammation in joints which directly reduces the pain of arthritis.

·       Diuretic: FL as a herb is known to act as a natural diuretic.

·       Cancer: Another advantage found in FL is that they can protect your body from getting vulnerable to cancer.

·       Weight loss: Leaves promote healthy weight loss.

·       Diarrhea: Infusion or decoction of FL is called "stomach tea and ant phlebitis tea" as it is used as herbal tea for the treatment of mild diarrhoea and also promotes flushing of urine.

 

2.1 Carrissa caronda Leaves:

Also known as Karamarda in Sanskrit, Carissa carandas (CC) belongs to the family- Apocynaceae. It is a large evergreen shrub with short and glabrous stem, bark light grey and scaly branches usually in alternate fashion. Its leaves are simple, opposite, generally 2-3 cm x 1-1.5 cm, ovate with short petiole measuring about 3-6 mm long and has leathery glabrous texture (coriaceous). The color of leaves is green with shine on the upper surface whereas the lower surface has a dull green shade. The leaves are oblong and conical in shape. ^13-14.

 

CCL showed the presence of several active chemical constituents including phenolic compounds, flavonoids, phenolic acids, tannins, lignin, and alkaloids ¹⁵. Traditionally and ethnomedicinally is used for numerous treatments like:

 

·       Wound healing: The paste prepared from the leaf is applied over fresh wounds for its treatment^.16

 

·       Anti-bacterial actions: Cold aqueous, methanol, ethanol, ethyl acetate extracts of leaves of CC in a final concentration of 500mg/ml were evaluated for their antibacterial properties against some selected pathogenic microorganisms such as Pseudomonas aeruginosa ^17.

 

·       Leprosy: Extract of CCL is used to treat leprosy ¹⁸.

·       Others: Leaf decoctions are used in the treatment of remittent fever, diarrhoea, earache, mouth and throat soreness, and syphilitic pains ¹⁹.

 

Carissic acid methyl ester an isomer of ursolic acid was isolated from CCL in 1988 by Naim Z et al. He also isolated Carissic acid monoacetate from leaves ^[20]. A new triterpene “carandinol” was isolated from the leaves of CC, along with five known compounds, betulinic acid, b-sitosterol-3-O-b-D-glucopyranoside, oleanolic acid, ursolic acid and 4-hydroxybenzoic acid ²¹.

 

Table-1: FL and CCL chemical constituents and their activity.

Leaf Name	Chemical Constituents	Activity	References
Fragaria leaves	Phenolic Compounds	Anti -inflammatory	21
	Ellagic acids (EA)	Anti-oxidant	22
	Anthocyanin	Anti-inflammatory	23
	Quercetin	Anti-oxidant and Anti-inflammatory	24
	Kaempferol	Anti-oxidant	25
Carrissa Caronda leaves	Carissic acid	Anti-inflammatory, anti-oxidant, analgesic, anti-convulsant and in neuropharamacological activities.	26
	Carandinol	Anti-convulsant, immunomodulatory and antiglycation.	27
	Betulinic acid	Anti-tumour.	28
	Oleanolic acid	Hepatoprotective.	29
	Ursolic acid	Anti-proliferative.	30

 

2.3 Fragaria and Carissa carandas Leaves in Mental Disordrer:

Depression, a mental disorder is one of the serious diseases prevailing all over the world affecting 13–20% population ^[31]. As resistance is developed with the drugs already available in the market plants-based drugs prove to be an effective approach for new antidepressant agents that act via different mechanisms ^32..

 

 

 

3. Psychological, Behavioral and Pharmacological Changes in Post-Traumatic Stress Disorder:

Up to 80% of all acute stress disorders develop into PTSD. It has been postulated that the development of behaviour problems and PTS symptoms may be influenced by age at the time of the traumatic event, particularly if it occurs during a developmentally sensitive period ⁹⁰. Some Psychological and behavioural changes that patient suffer is: ³³

·       Inability to remember some aspects of the event

·       Feelings of guilt and blame, Having a reduced interest in life

·       Feeling detached and estranged from others and emotionally and mentally numbed

Pharmacologically different animal models (figure-4) of PTSD have been developed for neuro-pathophysiology and pharmacological evaluations ³⁴.

 

Figure. 3: Different PTSD models.

 

4. Marketed Formulation for Ptsd and Mental Disorder:

PTSD can be either acute or chronic. In those with acute PTSD, symptoms last for at least 1 month but less than 3 months after the traumatic event. In chronic PTSD, symptoms last for more than 3 months after exposure to trauma ^[35]. At the same time, there is also evidence that other treatment modalities, such as psychodynamic psychotherapy, hypnotherapy, eye movement desensitization and reprocessing can be effective as well; albeit their evidence is derived from less numerous and less well-controlled studies (i.e., open trials or case reports) ^36.

 

Table. 2: Marketed formulation for PTSD and Mental Disorder.

Sr no.	Name of drug	Class of drug	Brand name	Company and Reference
1.	CC	Polyphenol	Flavurin	Flaviva 37
2.	Ashwagandha	Steroidal Alkaloid	Stresscom	Dabur 38

 

 

Doctors usually prescribe medications that affect the neurotransmitters serotonin or norepinephrine SSRIs and SNRIs. Another antidepressant that is commonly used is bupropion. Bupropion is a third type of antidepressant that works differently than either SSRIs or SNRIs³⁸.

 

5. Recent work on Fragaria, Carissa carandas and PTSD:

The table no. 3 below presents the recent work, or purpose statement, about Fragaria, Carissa carandas and PTSD, the information was gathered from a variety of sources. This may be useful for future researchers, industries, or even for patients suffering from PTSD.

 

Table. 3: Recent work by various researches on Fragaria, Carissa Carandas and PTSD

Application	Study	Model/drug category	Research Approach	Conclusion and Reference
Diagnosis of PTSD	Assessment of a new self-rating scale for PTSD.	Davidson Trauma Scale	Davidson Trauma Scale (DTS), a 17-item scale measuring each DSM-IV symptom of PTSD on 5-point frequency and severity scales. Other scales were also included as validity checks.	The DTS showed good reliability and validity and offers promise as a scale that is particularly suited to assessing symptom severity, treatment outcome and in screening for the likely diagnosis of PTSD .

 

6. CONCLUSION AND DISCUSSION:

PTSD is a mental health problem that some people develop after witnessing a life-threatening situation such as combat, a catastrophic event, a serious accident, or sexual assault. It is associated with a variety of psychiatric issues, namely depression, anxiety disorders, and drug abuse issues.  As per empirical evidence, people with severe mental disorders are much more likely than the general population to be exposed to stressful events during their lifetime. Thus, several researchers have evaluated the neuroprotective activity of CC and FL. Quercetin, kaempferol, carissic acid, EA and various polyphenolic compounds have high antioxidant potential and are extracted from CC and FL. Also, in some experiments rats were maintained on antioxidant diets comprising strawberry extracts which concluded it can mitigate the occurrence of neurochemical and behavioural changes. CC and FL extracts are proved effective in in-vitro and in-vivo experiments to combat PTSD and thus can be tested for clinical trials to evaluate its safety and efficacy on humans and will be beneficial for reducing the adverse events of synthetic medications.

 

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Accepted on 13.04.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(11):5344-5348.