Role of Nitric Oxide Modulators in Neuroprotective Effects of Mangiferin in 6-Hydroxydopamine-induced Parkinson's Disease in Rats.

Background: Parkinson's disease (PD) is typified by inflammation of dopaminergic neurons leading to the release of various inflammatory mediators. These mediators activate the transcription factor NF-κB, which in turn activates inducible nitric oxide synthase (iNOS), leading to increased inflammation. Purpose: This study was intended to study the effect of combination of mangiferin, a specific inhibitor of NF-κB with low-dose nitric oxide (NO) modulators. Methods: A total of eight Wistar rats weighing 200-250 g were used in each group. Stereotactic surgery was performed to induce 6-hydroxydopamine (6-OHDA) lesions. The treatment period extended from day 14 to day 42, during which time behavioral tests were performed to evaluate the effects of mangiferin and its combination with NO modulators. On day 42, the brains of the rats were removed for biochemical and molecular analyzes. Results: Mangiferin significantly improved locomotor activity and decreased inflammatory chemokines levels in rats with 6-OHDA lesions. Mangiferin therapy decreased myeloperoxidase (MPO) levels and reduced oxidative stress. In particular, caspase-3, caspase-9 and COX-2 activities were significantly reduced after the mangiferin treatment. A combination of 45-µg mangiferin and 10-mg/kg L-NAME showed the greatest improvement in locomotor, behavioral, biochemical, and molecular parameters impaired by 6-OHDA. Conclusion: In this study, mangiferin was found to protect rats with 6-OHDA lesions by inhibiting inflammation causing chemokines such as TNF-α and IL-6. Besides, the grouping of iNOS inhibitor L-NAME at a dose of 10 mg/kg with 45-µg mangiferin enhanced the anti-inflammatory and anti-Parkinsonian activity of mangiferin. Consequently, the combination therapy of mangiferin and L-NAME is promising for the treatment of PD. However, clinical trials will be required to evaluate the efficacy of this combination therapy in humans.

Artificial intelligence revolutionizing drug development: Exploring opportunities and challenges.

By harnessing artificial intelligence (AI) algorithms and machine learning techniques, the entire drug discovery process stands to undergo a profound transformation, offering a myriad of advantages. Foremost among these is the ability of AI to conduct swift and efficient screenings of expansive compound libraries, significantly augmenting the identification of potential drug candidates. Moreover, AI algorithms can prove instrumental in predicting the efficacy and safety profiles of candidate compounds, thus endowing invaluable insights and reducing reliance on extensive preclinical and clinical testing. This predictive capacity of AI has the potential to streamline the drug development pipeline and enhance the success rate of clinical trials, ultimately resulting in the emergence of more efficacious and safer therapeutic agents. However, the deployment of AI in drug discovery introduces certain challenges that warrant attention. A primary hurdle entails the imperative acquisition of high-quality and diverse data. Furthermore, ensuring the interpretability of AI models assumes critical importance in securing regulatory endorsement and cultivating trust within scientific and medical communities. Addressing ethical considerations, including data privacy and mitigating bias, represents an additional momentous challenge, requiring assiduous navigation. In this review, we provide an intricate and comprehensive overview of the multifaceted challenges intrinsic to conventional drug development paradigms, while simultaneously interrogating the efficacy of AI in effectively surmounting these formidable obstacles.

Comparative analysis of the efficiency of seed protein profiles in assessing genetic variation and population structure among indigenous Manipur black rice cultivars.

BACKGROUND: The state of Manipur, North East India has distinct topology of hill and valley regions with vast agroclimatic variability, being considered as one of the centers of rice diversity. The indigenous Manipur black rice cultivars exhibit wide range of diversity in morphology, pericarp color, shape and size of grain, aroma, glutinous or non-glutinous features but remain less characterised. Many of these cultivars, such as those named Chakhao, are endowed with multiple health benefits due to high anthocyanins, and hold special importance for the local people. It is important to analyse the genetic diversity and population structure for this germplasm with unique allelic combinations to utilize in rice breeding programme. METHODS AND RESULTS: We characterized total soluble seed protein fractions to not only fingerprint the 45 indigenous black rice cultivars but assess their genetic relatedness. Cluster analyses generated mainly two groups, complemented by PCoA scatter plot ascertaining geographical distinction. The hill black rice were more diverse. The population structure analysis revealed seven subpopulations indicating high genetic variability. The 24 polymorphic bands were scored in the range of 127.8 to 10.3 kDa comprised of four protein fractions. Three polypeptide bands each were ascribed to known fractions of glutelins and prolamins, while one band each could be described for albumin and globulin fractions, besides other diagnostic bands. CONCLUSION: Some diverse cultivars were Amubi, Chedo Anal, Chipi Buh, Athebu, Poireton, BuPu Mui, Kotha Chahao II. These cultivars can be used in future black rice breeding programmes. This can further prevent genetic erosion and protect intellectual property rights.

Anti-oxidative and anti-neuroinflammatory role of Necrostatin-1s and docosahexaenoic acid in RIP-1-mediated neurotoxicity in MPTP-induced Parkinson's disease model.

Parkinson's disease (PD) is a neuromuscular ailment that affects people in their later years and causes both motor and non-motor deficits. Receptor-interacting protein-1 (RIP-1) is a critical participant in necroptotic cell death, possibly through an oxidant-antioxidant imbalance and cytokine cascade activation in PD pathogenesis. The present study examined the role of RIP-1-mediated necroptosis and neuroinflammation in the MPTP-induced PD mouse model, as well as their protection by Necrostatin-1s (an RIP signalling inhibitor), antioxidant DHA and their functional interaction. BALB/c mice were given acute MPTP therapy (4 injections of 15 mg/kg i.p. at 2-h intervals) on day 1. After MPTP intoxication, Necrostatin-1s (Nec-1s; 8 mg/kg/day, i.p.) and DHA (300 mg/kg/day, p.o.) treatments were given once daily for 7 days. The Nec-1s treatment prevented MPTP-induced behavioural, biochemical and neurochemical alterations, and the addition of DHA increases Nec-1s' neuroprotective impact. In addition, Nec-1s and DHA significantly improve the survival of TH-positive dopaminergic neurons and lower expression levels of the inflammatory cytokines, IL-1ß and TNF-α. Furthermore, Nec-1s dramatically reduced RIP-1 expression, whereas DHA had little effect. Our research raises the possibility that neuroinflammatory signalling and acute MPTP-induced necroptosis are both mediated by TNFR1-driven RIP-1 activity. In this study, RIP-1 ablation through Nec-1s and the addition of DHA showed a reduction in the levels of pro-inflammatory and oxidative markers, as well as protection from MPTP-driven dopaminergic degeneration and neurobehavioural changes, suggesting potential therapeutic applications. For a better understanding, additional research about the mechanism(s) behind Nec-1s and DHA is required.

Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson's disease.

Parkinson's disease (PD) is a neuro-motor ailment that strikes adults in their older life and results in both motor and non-motor impairments. In neuronal and glial cells, PD has recently been linked to a dysregulated autophagic system and cerebral inflammation. Chloroquine (CQ), an anti-malarial drug, has been demonstrated to suppress autophagy in a variety of diseases, including cerebral ischemia, Alzheimer's disease (AD), and Traumatic brain injury (TBI), while its involvement in PD is still unclear. BALB/c mice were randomly allocated to one of four groups: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), CQ treatment with or without MPTP, or control. The CQ treatment group received CQ (intraperitoneally, 8 mg/kg body weight) after 1 h of MPTP induction on day 1, and it lasted for 7 days. CQ therapy preserves dopamine levels stable, inhibits tyrosine hydroxylase (TH) positive dopaminergic cell death, and lowers oxidative stress. CQ reduces the behavioural, motor, and cognitive deficits caused by MPTP after injury. Furthermore, CQ therapy slowed aberrant neuronal autophagy (microtubule-associated protein-1 light chain 3B; LC3B & Beclin1) and lowered expression levels of the inflammatory cytokines interleukin 1 (IL-1ß) and tumour necrosis factor (TNF-α) in the mice brain. In addition, CQ's antioxidant and anti-inflammatory effects were also tested in MPTP-mediated cell death in PC12 cells, demonstrating that CQ has a neurorestorative impact by successfully rescuing MPTP-induced ROS generation and cell loss. Our findings show that CQ's can help to prevent dopaminergic degeneration and improve neurological function after MPTP intoxication by lowering the harmful effects of neuronal autophagy and cerebral inflammation.

Effects of mangiferin and its combination with nNOS inhibitor 7-nitro-indazole (7-NI) in 6-hydroxydopamine (6-OHDA) lesioned Parkinson's disease rats.

Nitric oxide (NO), generated by nitric oxide synthase enzymes (NOS), has an important role in maintaining synapse plasticity, neuro-modulation, and other physiological functions in the brain. NO thus generated also has a key role in formation of reactive oxygen and reactive nitrite species and subsequent neuronal damage due to sustained oxidative stress. Due to its property of ROS and RNOS generation, NO plays a significant role in Parkinson's disease (PD) pathogenesis. Therefore, we evaluated the effect of mangiferin alone and in combination with nNOS inhibitor 7-nitro-indazole (7-NI) in 6-OHDA lesioned rats. Male Wistar rats weighing 200-250 g (n = 8/group) were used in the study. Stereotactic surgeries of rats were done to induce 6-OHDA lesioning in rats. Then, treatment with mangiferin alone and in combination with 7-NI 10 mg/kg was done from days 14 to 42 for 28 days. On day 42, rats were subjected to behavioral studies, and their brains were taken out after euthanasia to perform biochemical and molecular studies. Treatment with mangiferin and 7-NI significantly increases locomotor parameters in 6-OHDA lesioned rats. Treatment with mangiferin 45 µg and 7-NI 10 mg/kg alone and in combination significantly reduces oxidative stress along with decrease in concentration of pro-inflammatory cytokines, cyclooxygenase 2, total nitrite (NOx) and FOS B concentration. Results of this study suggest that treatment with 7-NI 10 mg/kg further enhances anti-inflammatory and anti-parkinsonism activity of mangiferin owing to its property of inhibiting nNOS mediated FOS B signaling and thereby inhibiting mRNA formation of TNF-α and IL-6.

Intermittent Online Postdilution Hemodiafiltration versus High-Flux Hemodialysis in Non-critical Acute Kidney Injury: A Pilot Randomized Controlled Trial.

The preferential use of convective modes of hemodialysis (HD) for targeting hyper-cytokinemia state in sepsis-related acute kidney injury (AKI) has been questioned for its efficacy. Several studies have used predilution hemodiafiltration (HDF) in critically ill AKI patients with mixed results. In this study, we compared intermittent online postdilution HDF with the standard high-flux (HF) intermittent HD in non-critically ill patients with community-acquired (CA) AKI. In this pilot study, stable patients with CA AKI and systemic inflammatory response syndrome were included and given either postdilution online-HDF (OL-HDF) or standard HF HD outside intensive care units. The primary objectives were to assess the feasibility of conducting the study at a larger scale and to detect the differential impact of convective clearance on the rates of independence from dialysis at discharge or after 30 days. Plasma cytokine clearance was assessed as a secondary objective. Eighty consecutive AKI patients were randomized to receive dialysis in one of the treatment arms after fulfilling the eligibility criteria. The baseline parameters of clinical severity, etiology, and indications of dialysis, plus the baseline plasma cytokine profiles, were comparable. Moreover, 83% in the control arm and 71.1% in the intervention arm became independent from dialysis at discharge or at 30 days (P = 0.189). No survival advantage of postdilution OL-HDF was observed (P >0.05). Similar plasma cytokine clearance levels were noted in both arms. The current study confirms the feasibility; however, it does not support the preferential use of postdilution OL-HDF over HF-HD in non-critical patients.

Isolation and HPLC assisted quantification of two iridoid glycoside compounds and molecular DNA fingerprinting in critically endangered medicinal Picrorhiza kurroa Royle ex Benth: implications for conservation.

Picrorhiza kurroa is a medicinally important, high altitude perennial herb, endemic to the Himalayas. It possesses strong hepato-protective bioactivity that is contributed by two iridoid picroside compounds viz Picroside-I (P-I) and Picroside-II (P-II). Commercially, many P. kurroa based hepato-stimulatory Ayurvedic drug brands that use different proportions of P-I and P-II are available in the market. To identify genetically heterozygous and high yielding genotypes for multiplication, sustained use and conservation, it is essential to assess genetic and phytochemical diversity and understand the population structure of P. kurroa. In the present study, isolation and HPLC based quantification of picrosides P-I and P-II and molecular DNA fingerprinting using RAPD, AFLP and ISSR markers have been undertaken in 124 and 91 genotypes, respectively. The analyzed samples were collected from 10 natural P. kurroa Himalayan populations spread across four states (Jammu & Kashmir, Sikkim, Uttarakhand and Himachal Pradesh) of India. Genotypes used in this study covered around 1000 km geographical area of the total Indian Himalayan habitat range of P. kurroa. Significant quantitative variation ranging from 0.01 per cent to 4.15% for P-I, and from 0.01% to 3.18% in P-II picroside was observed in the analyzed samples. Three molecular DNA markers, RAPD (22 primers), ISSR (15 primers) and AFLP (07 primer combinations) also revealed a high level of genetic variation. The percentage polymorphism and effective number of alleles for RAPD, ISSR and AFLP analysis varied from 83.5%, 80.6% and 72.1%; 1.5722, 1.5787 and 1.5665, respectively. Further, the rate of gene flow (Nm) between populations was moderate for RAPD (0.8434), and AFLP (0.9882) and comparatively higher for ISSR (1.6093). Fst values were observed to be 0.56, 0.33, and 0.51 for RAPD, ISSR and AFLP markers, respectively. These values suggest that most of the observed genetic variation resided within populations. Neighbour joining (NJ), principal coordinate analysis (PCoA) and Bayesian based STRUCTURE grouped all the analyzed accessions into largely region-wise clusters and showed some inter-mixing between the populations, indicating the existence of distinct gene pools with limited gene flow/exchange. The present study has revealed a high level of genetic diversity in the analyzed populations. The analysis has resulted in identification of genetically diverse and high picrosides containing P. kurroa genotypes from Sainj, Dayara, Tungnath, Furkia, Parsuthach, Arampatri, Manvarsar, Kedarnath, Thangu and Temza in the Indian Himalayan region. The inferences generated in this study can be used to devise future resource management and conservation strategies in P. kurroa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00972-w.

Pharmacological, Biochemical and Immunological Studies on Protective Effect of Mangiferin in 6-Hydroxydopamine (6-OHDA)-Induced Parkinson's Disease in Rats.

Background: Parkinson's disease is a neurodegenerative disorder and is marked by inflammation and death of neurons in the striatum region of the midbrain. It has been reported that expression of NF-κB increases during Parkinson's disease, which promotes oxidative stress, stimulates release of proinflammatory cytokines, and induces expression of nitric oxide. Therefore, in this study, we have used mangiferin a specific NF-κB inhibitor. Mangiferin is a polyphenolic compound traditionally used for its antioxidant and anti-inflammatory properties. Methods: The study utilized male Wistar rats weighing 200-250 g (56 rats; n = 8/group). On day "0," stereotaxic surgery of rats was done to induce 6-hydroxydopamine lesioning in rats. Coordinates for substantia nigra were anteroposterior-2 mm, mediolateral-5 mm and dorsoventral-8.2 mm. After 14 days, those rats which show at least 210 contralateral rotations after administration of apomorphine (0.5 mg/kg S.C.) were selected for the study and were given treatment for 28 days. On day 28 of treatment, rats were subjected to behavioral studies to evaluate the effect of mangiferin and their brains were taken out after euthanasia to perform biochemical, molecular and immunological studies. Results: Treatment with mangiferin significantly improves the key parameters of locomotor activity and oxidative stress and reduces the parameters of inflammatory stress. Also, the activity of caspases was reduced. Significant decrease in activity of both cyclooxygenase 1 and 2 was also observed. Maximum improvement in all parameters was observed in rats treated with grouping of mangiferin 45 µg/kg and levodopa 10 mg/kg. Treatment with levodopa alone has no significant effect on biochemical and molecular parameters though it significantly improves behavioral parameters. Conclusion: Current treatment of Parkinson's disease does not target progression of Parkinson's disease. Results of this study suggest that mangiferin has protective effect in hemi-Parkinsonian rats. Therefore, the combination therapy of mangiferin and levodopa can be helpful in management of Parkinson's disease.

Pharmacological and biochemical studies on protective effects of mangiferin and its interaction with nitric oxide (NO) modulators in adjuvant-induced changes in arthritic parameters, inflammatory, and oxidative biomarkers in rats.

Current study was designed to evaluate protective effect of mangiferin and its interaction with low dose of nitric oxide (NO) modulators in complete Freund's adjuvant (CFA) inoculated rats. Male wistar rats (200-300 g, n = 8 per group) were used in the study. On day ''0'' of study arthritis was induced in rats by injecting 0.2 ml CFA in sub-planter region of right hind paw of animals. Treatment with methotrexate (5 mg/kg), mangiferin (10-30 mg/kg) alone and in combination with NO modulators was given (i.p.) from days 14 to 28. After 28 days, blood and joint synovial fluid was collected for biochemical analysis and rat paws were excised to estimate MDA and SOD in tissue (paw) homogenates. CFA inoculation significantly increases (1) arthritic index, (2) ankle diameter, (3) paw volume, and (4) serum TNF-α, IL-6, IL-1ß, and synovial TNF-α levels (p < 0.001). The serum Th1 (IFN-γ) and Th2 (IL-4) cytokine levels, MDA levels in rat paw tissue homogenates and serum NF-κB levels were also found significantly increased. Significant decrease in serum IL-10 levels and SOD activity was found after CFA inoculation. These CFA-induced arthritic changes, cytokine profile, and oxidative stress markers were significantly reversed by mangiferin (10-30 mg/kg) treatment alone and in combination with L-arginine and L-NAME nitric oxide modulators (p < 0.05). Treatment with methotrexate (5 mg/kg) also significantly reversed these adjuvant changes (p < 0.05). However, effect of methotrexate was less marked as compared to mangiferin (30 mg/kg) alone and in combination with L-NAME (10 mg/kg), but was comparable or slightly better than mangiferin (10 and 20 mg/kg). Thus, on the basis of our findings, we can suggest that interaction of mangiferin with nitric oxide modulators may have therapeutic value for chronic inflammatory disease such as RA.

ISSR markers for gender identification and genetic diagnosis of Hippophae rhamnoides ssp. turkestanica growing at high altitudes in Ladakh region (Jammu and Kashmir).

Hippophae rhamnoides L. ssp. turkestanica (Elaeagnaceae) is a predominantly dioecious and wind-pollinated medicinal plant species. The mature fruits of the species possess antioxidative, anti-inflammatory, antimicrobial, anticancerous, and antistimulatory properties that are believed to improve the immune system. The identification of male and female plants in H. rhamnoides ssp. turkestanica is quite difficult until flowering which usually takes 3-4 years or more. A sex-linked marker can be helpful in establishing the orchards through identification of genders at an early stage of development. Therefore, we studied the genetic diversity of populations in Ladakh with the aim to identify a gender-specific marker using ISSR markers. Fifty-eight ISSR primers were used to characterize the genome of H. rhamnoides ssp. turkestanica, of which eight primers generated 12 sex-specific fragments specific to one or more populations. The ISSR primer (P-45) produced a fragment which faithfully segregates all the males from the female plants across all the three valleys surveyed. This male-specific locus was converted into a SCAR. Forward and reverse primers designed from this fragment amplified a 750-bp sequence in males only, thus specifying it as an informative male-specific sex-linked marker. This SCAR marker was further validated for its capability to differentiate gender on an additional collection of plants, representing three geographically isolated valleys (Nubra, Suru, and Indus) from Ladakh region of India. The results confirmed sex-linked specificity of the marker suggesting that this conserved sequence at the Y chromosome is well preserved through the populations in Ladakh region. At present, there are no reliable markers which can differentiate male from female plants across all the three valleys of Ladakh region at an early stage of plant development. It is therefore envisaged that the developed SCAR marker shall provide a reliable molecular tool for early identification of the sex in this commercial crop. The genetic diversity of populations as surveyed by ISSR primers revealed 85.71 % polymorphism at the population level. The dendrogram obtained divided the genotypes into three different clusters, and the distribution of male and female genotypes in all the clusters was random. The Nei's genetic similarity index was in the range of 0.63-0.96.

Pharmacological studies on the anti-inflammatory and immunomodulatory role of pentoxifylline and its interaction with nitric oxide (NO) in experimental arthritis in rats.

AIM: Present study was designed to evaluate protective effects of pentoxifylline and its potentiation with low dose of nitric oxide (NO) modulators in adjuvant-induced experimental arthritis in rats. METHOD: Wistar rats (200-300 g, n = 8 per group) of both sexes were used in the study. On day "0" experimental arthritis was induced by injecting 0.2 ml of Complete Freund's adjuvant (CFA) in sub-planter region of right hind paw of animals. Pentoxifylline treatment alone and in combination with NO modulators was given (i.p.) from day 14 to 28. Various arthritic parameters were recorded and blood and joint synovial fluid was collected for biochemical analysis. RESULTS: CFA inoculation significantly increases (1) arthritic index (2) ankle diameter (3) paw volume (4) histopathology score (5) serum TNF-α, IL-6, IL-1ß and synovial TNF-α levels (p < 0.001) (6) serum Th1 and Th2 cytokine levels g) MDA levels in rat paw tissue homogenates (7) serum NF-κB levels. Significant decrease in serum IL-10 levels and SOD activity was observed in rats after CFA inoculation. Decrease in body weight and suppressed general quality of life of CFA inoculated rats was also observed. These CFA-induced arthritic changes were significantly reversed by pentoxifylline alone and in combination with low dose of NO modulators (p < 0.05). CONCLUSION: These results are suggestive of protective effects of pentoxifylline and its potentiation in combination with low dose of NO modulators. These results may provide new pharmacological therapy for management of rheumatoid arthritis (RA).

Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05).

Facultative apomixis and development of fruit in a deciduous shrub with medicinal and nutritional uses.

Knowledge of reproductive biology of plants is crucial to understand their natural mode of propagation, which may aid in conservation and crop improvement. The reproductive details are also crucial for beginning the cultivation of a potential crop on a commercial scale. Fruits of sea buckthorn, Hippophae rhamnoides, are used in a variety of medicinal and nutritional products. So far, fruits are collected from the female plants in the wild. It is known that the species fruits profusely and also propagates by forming root suckers, but the details of sexual reproduction are not available. We investigated the mode of reproduction and development of fruits from natural populations of sea buckthorn. Megasporogenesis and megagametogenesis were studied through resin-embedded sectioning and ovule-clearing methods, and fruit development through histochemistry. The study of mitosis and male meiosis showed that the plants at the site were diploid (2n = 2x = 24). The embryo sac may develop either through the monosporic pathway and differentiates into 'Polygonum type' or aposporously into 'Panicum type'. The embryo may develop by sexual and adventitious pathways. Thus, sea buckthorn is a facultative apomict. The occurrence of diverse reproductive pathways assures the possibility of generation of novel genotypes through sexuality, while apomictic reproduction maintains adaptive genotypes and ensures reproduction in the absence of pollination. Anatomical details suggest that the fruit of sea buckthorn may be appropriately described as a pseudo-drupe.