PHYTOCHEMICAL AND NEUROPHARMACOLOGICAL BASIS OF HIPPOPHAE SALICIFOLIA LEAVES IN ANXIETY DISORDERS: A REVIEW

PHYTOCHEMICAL AND NEUROPHARMACOLOGICAL BASIS OF HIPPOPHAE SALICIFOLIA LEAVES IN ANXIETY DISORDERS: A REVIEW

Abhyuday

Department of Pharmacology, Shambhunath Institute of Pharmacy, Jhalwa, Prayagraj, Uttar Pradesh, India.

ABSTRACT: Hippophae salicifolia D. Don, known as Himalayan Sea buckthorn, is a medicinal plant distributed in the Himalayan region. Based on available literature, this plant contains flavonoids, phenolic acids, tannins, triterpenoids, and antioxidant vitamins. Most research has been done on the fruit and seed oil. There is limited research published on the leaves and their pharmacological properties. The purpose of this review is to summarize the phytochemical and neuropharmacological activities of H. salicifolia leaves and evaluate their potential role in the management of anxiety disorders. The available literature systematically collected and reviewed to evaluate the phytochemical profile, experimental pharmacological evidence and possible mechanisms associated with the leaves of H. salicifolia. Studies on H. salicifolia leaves reported antioxidant, anti inflammatory, and adaptogenic effects. Some experimental reports also indicate that leaf extract may reduce changes in physiology related to chronic stress. As oxidative stress, neuroinflammation, and HPA-axis disturbance are linked to anxiety disorders, the phytochemicals present in the leaves may be relevant for neuropharmacological research. However, direct evidence supporting anxiolytic activity remains limited. The available data shows that H. salicifolia leaves may have potential effects on the nervous system and could serve as a promising source of bioactive compound in anxiety disorder. Still, we need pre-clinical studies and human trials to prove if they really work for anxiety and to understand how they work.

Keywords: Hippophae salicifolia D. Don, Himalayan Sea Buckthorn, Anxiety, Neuroprotection, Neuropharmacology, Oxidative stress

INTRODUCTION: Anxiety disorders are common mental health problems across the world and affect millions of people. The main features of anxiety are persistent fear, excessive worry, and behavioral disturbances that interfere with normal daily life. Anxiety often coexists with depression, poor sleep and thinking problems, this makes management difficult and puts more load on health systems ¹.

Long term stress is major problem for anxiety. When stress goes on for long the HPA axis does not work normally. This leads to high cortisol for long time such hormonal changes can affect brain cells. It may also lead to changes in parts like hippocampus, amygdala and prefrontal cortex. These areas help to control emotions and thinking ^2-3.

Long stress also affects how the brain adapts it can cause changes in dendrites, less formation of new neurons and weak connections between neurons. This may lead to memory issues and emotional problems, and it can also increase the risk of anxiety ^2-4. Another point is oxidative stress. Long stress increases ROS in the body. This can damage lipids, proteins and DNA it may also disturb signals in neurons and mitochondria; inflammation is also involved in neuronal injury. Studies also reported that level of TNF-α, IL-1β, and IL-6 also increase in anxiety ^5-7.

Anxiety disorders are linked to chemical imbalances in the brain involving serotonin, dopamine, and GABA systems disrupt normal mood which regulate and enhance anxiety responses. But standard pharmacological agents such as benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) act on these pathways, their prolonged administration is restricted because of undesirable effects, tolerance, dependence, and withdrawal symptoms ^8-9.

Regular anti-anxiety drugs come with a lot of drawbacks. That’s why researchers are now looking at medicinal plants as an alternative. Plant compounds are being studied a lot for brain and mental health problems. Most of the focus right now is on phytochemicals like flavonoids and phenolic compounds. They’re strong antioxidants, anti-inflammatory and they help protect nerve cells These bioactive constituents not only clearing free radicals but also regulate intracellular signaling pathways involved in neuronal survival, synaptic plasticity, and inflammation, thereby offering a multi-targeted approach for anxiety management ¹⁰.

Hippophae salicifolia D. Don, or Himalayan Sea Buckthorn leaves have a lot of active compounds flavonoids, phenols, tannins, and antioxidant vitamins. Experimental investigations show that leaf extracts act as antioxidants, anti-inflammatory, antimicrobials, and Adaptogens. Some early animal studies also suggest they may help reverse the body changes caused by chronic stress. Studies on anxiolytic potential of H. salicifolia leaf extracts remain scarce. More pharmacological investigations are required to clarify their neuroprotective potential and therapeutic significance in anxiety management ^11-15.

Traditional Medicinal uses of Hippophae salicifolia: In the traditional healthcare systems of the Himalayan region, Hippophae salicifolia has been used for a variety of medicinal purposes. Ethnobotanical reports indicate that its leaves and fruits are commonly employed for relieving headache, severe cold, cough and throat infections. Berry oil has traditionally been used for managing gastritis, ulcers and certain gynecological infections, while bark ash has been applied to burn wounds and diarrhoea. In addition, berries have also been used in veterinary medicine, highlighting the broad ethnomedicinal importance of this species ¹¹.

Phytochemical Profile: The leaf material of Hippophae salicifolia D. Don contains a wide range of biologically active phytochemicals, particularly flavonoids, flavonols, phenolic acids, tannins, flavone glycosides, and other polyphenolic molecules. Recent LC-MS investigation revealed numerous phytochemicals that are responsible for the plants antioxidants, anti inflammatory, antimicrobial, and potential neuroprotective activities. The broad spectrum of these phytoconstituents suggests that H. salicifolia leaves may represent a valuable natural source of therapeutic agents for managing oxidative stresses-related disorders and other chronic diseases ¹⁵.

Flavonoids and Flavonols: Flavonoids constitute one of the predominant groups of phytochemicals in H. salicifolia leaves. LC-MS analysis has detected several flavonoids including quercetin, kaempferol-3-O-rhamnoside, isorhamnetin, dihexosylisorhamnetin, 6-hydroxyluteolin-7-rhamnoside, apigenin 4′-O-rhamnoside, and apigenin 6,8-di-C-glucoside. These flavonoids are reported to possess potent antioxidant capacity and may help neutralizing reactive oxygen species (ROS) they also suggested to contribute to the overall pharmacological potential of the plant ^{13, 15}.

Phenolic Acids: Phenolic acids represent another important class of bioactive constituent present in H. salicifolia. The principle phenolic acids identified include chlorogenic acid, quinic acid, caffeoyl-2-hydroxyethane-1,1,2-tricarboxylic acid, and 3-p-coumaroylquinic acid. These phenolic constituents demonstrate both antioxidant and anti-inflammatory activities and also known to protect cellular components from oxidative damage and contribute to overall tissue protection ¹⁵.

Catechins and Polyphenolic Compounds: Several Catechin derivatives including epigallocatechin - 3 - O - gallate (EGCG), methylgalloyl epicatechin, and 3′-O-methylcatechin have been identified in H. salicifolia leaves. These Catechins exhibit strong antioxidant capacity and may help to neutralize free radicals and protecting cells against oxidative injury. Catechins are also associated with anti-inflammatory and cardio protective effects, contributing significantly to the pharmacological potential of sea buckthorn leaves ¹⁵.

Tannins and Galloyl Derivatives: The leaves of H. salicifolia contain tannins and galloyl derivatives such as pedunculagin and dimethyl galloyl hexoside. Tannins possess strong antioxidant activity because of their efficient hydrogen donating capacity to neutralize free radicals. These phytoconstituents help preserve membrane integrity, minimize oxidative injury, and improve cellular resistance during pathological conditions ¹³.

The pharmacological significance of H. salicifolia leaves can be attributed to the combined action of flavonoids, phenolic acids, tannins, and other polyphenols. These compounds collectively target multiple biochemical pathways involved in oxidative stress, inflammation, cellular injury, and metabolic dysfunction. Such a multi-targeted mechanism may explain the traditional and experimentally reported therapeutic benefits of H. salicifolia, including antioxidant, adaptogenic, and stress-protective effects ^{12, 14, 15}.

TABLE 1: PHYTOCONSTITUENTS OF H. SALICIFOLIA LEAVES

Source: Das M et al. 2026 ¹⁵

Pharmacological Activities: The leaves of Hippophae salicifolia possess diverse pharmacological activities owing to the presence of flavonoids, phenolic acids, flavonols, tannins and other polyphenolic compounds. These bioactive constituents contribute to antioxidant, anti inflammatory, adaptogenic and stress revealing activities that contribute to medical value of plant ^{11, 15}.

Antioxidant Activity: H. salicifolia leaf extracts demonstrate strong antioxidant potential. Due to the presence of quercetin, isorhamnetin, chlorogenic acid, kaempferol derivatives, and apigenin derivatives. These phytochemicals neutralizere active oxygen species, reduce oxidative damage, and strengthen endogenous antioxidant defense mechanisms, thereby maintaining cellular redox balance ^{12, 15}.

Anti-inflammatory Activity: Polyphenols and flavonoids present in the leaves regulate inflammatory signaling pathways and suppress the synthesis and release pro inflammatory mediators. This activity may help protect tissues from inflammation-induced damage ^{11, 15}.

Neuroprotective Activity: Flavonoids, Catechins and phenolic acids exhibit neuroprotective effects by lowering oxidative burden and protecting neuronal cells against oxidative injury ^14-15.

Adaptogenic and Anti-stress Activity: The leaves are rich in antioxidant phytochemicals that help improve cellular resistance against environmental and physiological stress. This adaptogenic effect may contribute to protection against stress-induced disorders ¹⁴.

Synergistic Multi-target Effects: The overall pharmacological activity of Hippophae salicifolia leaves is a result of the combined action of multiple bioactive compounds. These compounds work together to produce a broad protective effect against stress-induced damage, making them effective in targeting multiple aspects of neuropsychiatric disorders ^{11, 12, 14, 15}.

Overall, Hippophae salicifolia leaves exhibit multiple pharmacological activities that contribute to protection against stress-induced neuronal dysfunction. Their combined effects on oxidative stress, inflammation, neuronal health highlight their potential role in managing anxiety-related conditions.

Mechanism of Action of Major Phytochemicals Flavonoids: Flavonoids are one of the main group of phytochemicals founds in H. salicifolia leaves. These include derivatives of quercetin, kaempferol, isorhamnetin, apigenin and luteolin. Experimental studies show that some flavonoids such as apigenin can bind to the same site on GABA_A receptors where benzodiazepines work. However, H salicifolia contains apigenin derivatives rather than free apigenin. These compounds may contribute to similar pharmacological effects ^15-16, Quercetin has been found to reduce behavior changes caused by long term unpredictable stress. It does this by lowering oxidative damage and reducing inflammation in the hippocampus ^{15, 17}. Together, these effects on GABAergic signaling, oxidative stress and neuroinflammation may explain why flavonoids-rich extract of H. salicifolia could help with anxiety and protect nerve cells.

Catechins: Catechin derivatives, especially EGCG work mainly through antioxidant pathways. Studies report that EGCG can switch on the keep1/Nrf2 signaling pathway. This leads to higher production of the body’s own antioxidant enzymes and lowers the level of reactive oxygen species inside cells and protects nerve cells from oxidative damage. Because of this, EGCG helps to keep the cells redox balance stables and may reduce brain cell damage caused by long term stress ¹⁸.

Phenolic Acids: Phenolic acids, especially chlorogenic acid are known for their antioxidant effects and help to control the cellular redox balance. Research shows that chlorogenic acid activates the Nrf2-ARE pathway and also directly cleanup the reactive oxygen species. When this pathway is activated, the cells’ antioxidant defense gets stronger and oxidative damage to nerve tissue is reduced. In this way, phenolic acids may help to protect brain function during long period of oxidative stress ¹⁹.

Tannins: Hydrolysable tannins such as pedunculagin have strong antioxidant and anti-inflammatory effects. Evidence suggests they can neutralize ROS, block lipid peroxidation and calm down inflammatory processes. This protects cells from oxidative injury. While there isn’t much direct proof yet that they reduce anxiety, their ability to lower the oxidative stress and inflammation may still help to keep neuron healthy under stress related conditions ²⁰.

Relevance to Anxiety Disorders: There isn’t just one reason behind anxiety disorders. They usually develop when hormone balance, oxidative stress, inflammation, and brain chemicals all get disturbed together. Disturbances in the hypothalamic pituitary adrenal (HPA) axis, increased oxidative stress, and elevated inflammatory mediators collectively contribute to neuronal dysfunction and behavioral abnormalities ^{2, 7}.

Anxiety disorders are frequently linked to oxidative imbalance neuroinflammation, and neuronal dysfunction. Recent phytochemical investigations of Hippophae salicifolia leaves have revealed the presence of several bioactive compounds including quercetin, isorhamnetin, kaempferol derivatives, chlorogenic acid, apigenin derivatives, and other polyphenolic constituents. These compounds are known as antioxidants and brain protectors. That may help reduce oxidative damage and maintain neuronal function ^{11, 12, 14, 15}.

Animal studies have also shown that H. salicifolia leaf extracts can protect against stress and act as Adaptogens during long-term stress. Since oxidative stress and prolonged stress exposure are important factors involved in the initiation and advancement of anxiety disorders, the phytochemical composition and stress-modulating properties of H. salicifolia suggest its potential relevance in anxiety management ^{12, 14, 15}.

But direct studies evaluating the anxiolytic activity of H. salicifolia leaves are limited, the available evidence provides a scientific rationale for further investigation of its therapeutic significance in anxiety and other stress related neuropsychiatric disorders.

DISCUSSION: Hippophae salicifolia leaves have gained attention for both their chemistry and medicinal potential. Work so far shows the leaves are rich in flavonoids, flavonols, phenolic acids, flavanols and tannins. These phytochemicals contribute to the pharmacological potential of H. salicifolia leaves ^{13, 15}.

A big reason for this interest is the plant’s antioxidant capacity. The phytochemicals in it can reduce reactive oxygen species, decrease oxidative damage, and keep cells from getting injured ¹³. There’s also evidence that H. salicifolia helps the body cope with long-term stress. It appears to have adaptogenic and stress-protective properties that may help restore balance when stress goes on for a long time ¹⁴.

Since oxidative stress plays a part in anxiety, these compounds could potentially protect nerve cells. But we don’t have many direct studies yet on whether H. salicifolia leaves actually work as an anxiolytic. However additional well designed experimental studies are required to establish the anxiolytic potential of H. salcifolia ^14-15.

Taken together, the data suggest H. salicifolia leaves contain useful bioactive compounds. Their antioxidant and stress-buffering effects make them a candidate worth exploring for anxiety and other stress-related problems ^{11, 15}.

Research GAP: Hippophae salicifolia has been getting more attention from researchers, but lots of things still unknown. Most studies till now have focused on what’s inside the leaves, like its chemicals, antioxidant capacity, germ-fighting ability, blood sugar effects, and stress-buffering properties. When it comes to anxiety, not much work has been done ^{13, 15}.

The bigger problem is that we’re missing proper animal studies. Standard tests used for anxiety such as the Elevated Plus Maze ²¹, Open Field Test ²², Light Dark Box ²³, and Hole Board Test ²⁴, have barely been applied to H. salicifolia leaf extracts. Without that data, we can’t really say if it helps with anxiety ²⁵. Current understanding of the neurochemical mechanisms responsible for its possible anxiolytic activity is also incomplete. We know the leaves contain flavonoids, phenolic acids and other antioxidants. But we don’t know yet how these compounds interact with the brain signals involved in anxiety. There are other missing pieces as well. The right dose hasn’t been worked out. We don’t know how it moves through the body. And there’s no information yet on long-term safety or whether it actually works in humans. Therefore, additional preclinical investigations followed by well designed clinical studies are necessary to determine the therapeutic value of H. salicifolia as a natural investigation for anxiety disorders.

Future Perspectives: In future researchers should properly test if H. salicifolia leaves can reduce anxiety. This means running standard animal tests like the Elevated Plus Maze, Open Field Test, Light Dark Box and similar models. That kind of data will give us a clearer answer about whether it actually helps with anxiety disorders.

We also need to figure out which compounds in the plant are doing the work. Once we know that, we can understand better how they protect nerve cells and help the body handle stress. Other important things to check are the right dose, how the body absorbs and removes it, safety in short-term use, and any problems from using it for a long time. In the end, human trials will be needed. Only then can we confirm if H. salicifolia can be used as a plant-based option for managing anxiety.

CONCLUSION: Hippophae salicifolia leaves have a lot of active plant compounds. They contain flavonoids, phenolic acids, tannins and other polyphenols. Together, these compounds can fight oxidation, help the body manage stress, and support brain cell health. Because of this, the plant looks useful from a medical point of view. Early data also suggests they may lower oxidative damage and help keep the nerve function normally. We don’t have direct proof, yet that H. salicifolia works for anxiety. But based on what’s in the leaves and what we know about its effects, it seems like a good candidate to study further for anxiety-related problems. More lab work and human studies are needed now. That’s the only way to confirm if it’s safe, if it actually works, and if it can be used as a treatment.

ACKNOWLEDGEMENT: The author is thankful to Shambhunath Institute of Pharmacy, Prayagraj, Uttar Pradesh, India for academic support.

CONFLICT OF INTEREST: The author declares that there is no conflict of interest.

REFERENCES:

1. Baxter AJ, Scott KM, Vos T and Whiteford HA: Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychol Med 2013; 43(5): 897-910. doi:10.1017/S003329171200147X.
2. McEwen BS: Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 2007; 87(3): 873-904. doi:10.1152/physrev.00041.2006.
3. Lupien SJ, McEwen BS, Gunnar MR and Heim C: Effects of stress throughout the lifespan on the brain, be-haviour and cognition. Nat Rev Neurosci 2009; 10(6): 434-445. doi:10.1038/nrn2639.
4. Joëls M, Pu Z, Wiegert O, Oitzl MS and Krugers HJ: Learning under stress: how does it work? Trends Cogn Sci 2006; 10(4): 152-158. doi:10.1016/j.tics.2006.02.002.
5. Michopoulos V, Powers A, Gillespie CF, Ressler KJ and Jovanovic T: Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology 2017; 42(1): 254-270. doi:10.1038/npp.2016.146.
6. Salim S: Oxidative stress and psychological disorders. Curr Neuropharmacol 2014; 12(2): 140-147. doi:10.2174/1570159X11666131120230309.
7. Dantzer R, O'Connor JC, Freund GG, Johnson RW and Kelley KW: From inflammation to sickness and de-pression: when the immune system subjugates the brain. Nat Rev Neurosci 2008; 9(1): 46-56. doi:10.1038/nrn2297.
8. Kalueff AV and Nutt DJ: Role of GABA in anxiety and depression. Depress Anxiety 2007; 24(7): 495-517. doi:10.1002/da.20262.
9. Ressler KJ and Nemeroff CB: Role of serotonergic and noradrenergic systems in the pathophysiology of de-pression and anxiety disorders. Depress Anxiety 2000; 12(1): 2-19. doi:10.1002/1520-6394(2000)12:1+<2:AID-DA2>3.0.CO;2-4.
10. Sarris J, Panossian A, Schweitzer I, Stough C and Scholey A: Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol 2011; 21(12): 841-860. doi:10.1016/j.euroneuro.2011.04.002.
11. Ranjana S, Goyal A, Jena G and Tikoo K: Hippophae salicifolia Don, a fascinating medicinal plant: an update on its traditional medicinal uses, ethnopharmacology and phytochemistry. Curr Tradit Med 2022; 8(2). doi:10.2174/2215083808666220527144311.
12. Goyal AK, Basistha BC, Sen A and Middha SK: Antioxidant profiling of Hippophae salicifolia growing in sacred forests of Sikkim, India. Funct Plant Biol 2011; 38(9): 697-709.
13. Ilango K, Kasthuri Bai N, Mohan Kumar R, Ananth Kumar K, Dubey GP and Agrawal A: Pharmacognostic studies on the leaves of Hippophae rhamnoides and Hippophae salicifolia D. Don. Res J Med Plants 2013; 7(1): 58-67. doi:10.3923/rjmp.2013.58.67.
14. Rathor R, Sharma P, Suryakumar G and Ganju L: A pharmacological investigation of Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) against multiple stress (C-H-R): an experimental study using rat model. Cell Stress Chaperones 2015; 20(5): 821-831. doi:10.1007/s12192-015-0603-2.
15. Das M, Gogoi BJ, Bora A and Raju NL: Phytochemical analysis, in-vitro anti-oxidant, anti-diabetic, and an-tibacterial activities of leaf extracts of Hippophae salicifolia from North East India. Food Wellness 2026; 2(1): 100040. doi:10.1016/j.foodw.2026.100040.
16. Wasowski C and Marder M: Flavonoids as GABAA receptor ligands: the whole story? J Exp Pharmacol 2012; 4: 9-24. doi:10.2147/JEP.S23105.
17. Mehta V, Parashar A and Udayabanu M: Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress. Physiol Behav 2017; 171: 69-78. doi:10.1016/j.physbeh.2017.01.006
18. Yao J, Peng S, Xu J and Fang J: Reversing ROS-mediated neurotoxicity by chlorogenic acid involves its direct antioxidant activity and activation of Nrf2-ARE signaling pathway. Bio Factors 2019; 45(4): 616–626. doi:10.1002/biof.1507.
19. Tang S, Zhang Y and Botchway BOA: Epigallocatechin-3-Gallate Inhibits Oxidative Stress Through the Keap1/Nrf2 Signaling Pathway to Improve Alzheimer Disease. Molecular Neurobiology 2025; 62(3): 3493–3507. doi:10.1007/s12035-024-04498-6
20. Snarska J, Jakimiuk K and Strawa JW: A Comprehensive Review of Pedunculagin: Sources, Chemi-stry, Biological and Pharmacological Insights. Int J Mol Sci 2024; 25(21): 11511. doi:10.3390/ijms252111511.
21. Pellow S, Chopin P, File SE and Briley M: Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985; 14(3): 149-167. doi:10.1016/0165-0270(85)90031-7.
22. Prut L and Belzung C: The open field as a paradigm to measure the effects of drugs on anxiety-like beha-viors: a review. Eur J Pharmacol 2003; 463(1–3): 3–33. doi:10.1016/S0014-2999(03)01272-X.
23. Bourin M and Hascoët M: The mouse light/dark box test. Eur J Pharmacol 2003; 463(1-3): 55-65. doi:10.1016/S0014-2999(03)01274-3.
24. File SE and Wardill AG: Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacologia 1975; 44(1): 53–59. doi:10.1007/BF00421184.
25. Himanshu, Dharmila, Sarkar D and Nutan: A review of behavioral tests to evaluate different types of anxiety and anti-anxiety effects. Clin Psychopharmacol Neurosci 2020; 18(3): 341-351. doi:10.9758/cpn.2020.18.3.341
    

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    How to cite this article:

    Abhyuday: Phytochemical and neuropharmacological basis of Hippophae salicifolia leaves in anxiety disorders: a review. Int J Pharmacognosy 2026; 13(10): 1021-26. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.13(10).1021-26.

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